Cold Spring Harbor Symposia on Quantitative Biology

Home , Andrew Huxley, Hugh Huxley, Meromyosin

COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XXXVII COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

Founded in 1933 by REGINALD G. HARRIS Director of the Biological Laboratory 1924 to 1936

LIST OF PREVIOUS VOLU.~IES

Vo]ume i (1933) Surface Phenomena Volume II (1934) Aspects of Growth Volulne III (1935) Photochemical Reactions Volume IV (1936) Excitation Phenomena Volume V (1937) Internal Secretions Volume VI (1938) Protein Chemistry Volume VII (1939) Biological Oxidations Volume VIH (1940) Permeability and the Nature of Cell Membranes Volume IX (1941) Genes and Chromosomes. Structure and Organization Volume X (1942) The Relation of Hormones to Development Volume XI (1946) Heredity and Variation in Microorganisms Volume XII (1947) Nucleic Acids and Nucleoproteins Volume XIII (1948) Biological Applications of Tracer Elements Volume XIV (1949) Amino Acids and Proteins Volume XV (1950) Origin and Evolution of Man Volume XVI (1951) Genes and Mutations Volume XVII (1952) The Neuron Volume XVIII (1953) Viruses Volume XIX (1954) The Mam,nalian Fetus: Physiological Aspects of Development Volume XX (1955) Population Genetics: The Nature and Causes of Genetic Variability in Population Volume XXI (1956) Genetic Mechanisms: Structure and Function Volume XX[I (1957) Population Studies: Animal Ecology and Demography Volume XXIII (1958) Exchange of Genetic 3Iatcrial: Mechanism and Consequences Volume XXIV (1959) Genetics and Twentieth Century Darwinism Volume XXV (1960) Biological Clocks Volume XXV [ (1961 ) Cellular Regulatory l~Ieehanisms Volume XXVII (1962) Basic Mechanisms in Animal Virus Biology Volume XXVIII (1963) Synthesis and Structure of Macro,nolecules Volume XXIX (1964) Human Geuetics Volume XXX (1965) Sensory Receptors Volume XXXI (1966) The Genetic Code Volume XXXII (1967) Antibodies, Volume XXXI[I (1968) P~eplication of DNA in Microorganisms Volumc XXXIV (1969) The Mechanism of Protein Synthesis Volume XXXV (1970) Transcription of Genetic Material Volume XXXVI (1971) Structure and Function of Proteins at the Three-di,nensional Level COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XXXVII

The Mechanism of Muscle Contraction

COLD SPRING HARBOR LABORATORY 1973 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XXXVH

Library of Congress Catalog Card Number 34-8174

P~nted in the United States of America

The Symposium Volumes are published by The Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, and may be purchased directly or through booksellers. Price of Volume 37--$30.00 (inc. postage). Price subject to change without notice. Symposium Participants

ABBOTT, ROGER H., Department of Zoology, ARC BRAY, DEN.'~IS, MRC Laboratory of Molecular Unit of Muscle Mechanisms, Oxfi)rd, England. Biology, Cambridge, England. ADELSTEIN, ROBERT S., National Heart and Lung BREMEL, ROBERT D., Department of Biochemistry, Institute, NIH, Bethesda, Md. St. Louis University School of Medicine, APRIL, ERNEST W., Department of Anatomy, St. Louis. College of Physicians and Surgeons, Columbia BULLARD, BELINDA, Department of Zoology, University, New York. Oxford University, Oxford, England. ARNDT, [SABELLE 0., Department of Anatomy, BURKE, MORRIS, Department of Biology, Johns University of Pennsylvania, Philadelphia. Hopkins University, Baltimore. Avis, VANCE R., Department of Physiology, Bt:TLER, THOMAS M., Department of' Animal University of California, Los Angeles. Biology, University of Pennsylvania Schoo] of BARANY, GEORGE, Department of Biochemistry, Veterinary Medicine, Philadelphia. The Rockefeller University, New York. BUZASII, ELIZABETII, Department of Biology, B~RXNY, KATE, Department of Physical Chemistry, University of Connecticut, Storrs. Institute for Muscle Disease, Inc., New York. CARLSON, FRA.~CIS l)., Department of Biophysics, B~-R~,NY, MIClIAEL,Department of Physical Chem- Johns Hopkins University, Baltimore. istry, Institute for Muscle Disease, |nc., CARNEY, HOWARD, JR., Department of Bio- New York. physics, Johns Hopkins University, Balti- BARTON, JA.'~ICE S., Department of Biology, more. Johns Hopkins University, Baltimore. CASPAR, DONALD L. O., Children's Cancer Research BASK1N, RONXLD J., Department of Zoology, Foundation, Boston. University of California, Davis. CIIEU.NG, HERBERT C., Department of Engineering BAss, BERL G., Department of Physiology, Biophysics, University of Alabama Medical Einstein College of Medicine, Bronx, New Center, Birmingham. York. CHOWRASHI,PROKAS]I K., Department of Anatomy, BENSON, ELLIS S., Department of Laboratory University of Pennsylvania Medical School, Medicine, University of Minnesota, Minnea- Philadelphia. polis. COItEN, CAROLYN, Children's Cancer Research BERNARDINI, [SA, Laboratory of Structural and Foundation, Boston. Molecular Biology, Children's Cancer Re- COLLINS, Jom~" H., Department of Muscle Research, search Foundation, Boston. Boston Biomedical Research Institute, Boston. BHATNAGAR, GI[Ot'AL, Department of Muscle COOKE, ROGER, Departments of Biochemistry and ]~esearch, Boston Biomedical Research insti- Biophysics, University of California, San tute, Boston. Francisco. Bin6, N. A., Biochemistry Group, EStvSs Ldr~nd COSTANTIN, LEROY L., Department of Physiology University, Budapest, Hungary. and Biophysics, Washington University School BOLAND, RlCARDO, Department of Biochemistry, of Medicine, St. Louis. St. Louis University School of Medicine, St. CUNNINGHAM, BRUCE A., Department of Bio- Louis. chemistry, The Rockefeller University, New BON.~ER, ROBERT F., Department of Biophysics, York. Johns Hopkins University, Baltimore. CVRTIN, Nancy, Department of Animal Biology, BRA~DT, PIIILIr W., Department. of Anatomy, University of Pennsylvania School of Veterin- Columbia University, New York. ary Medicine, Philadelphia. vi SYMPOSIUM PARTICIPANTS

DAVIES, ROBERT E., Department of Animal FISCHMAN, DONALD A., Department of Biology, Biology, University of Pennsylvania School of University of Chicago, Chicago. Veterinary Medicine, Philadelphia. FRASER, ALLAN, Department of Biophysics, Johns DAwsoN, JOAN, Department of Pharmacology, Hopkins University, Baltimore. University of Pennsylvania, Philadelphia. FRIEDMAN, ZVIEL, Department of Biochemistry, D'HAESE, JOCHEN, Department of Cytology and St. Louis University School of Medicine, St. Micromorphology, University of Bonn, Bonn, Louis. Germany. GAETJENS, ERIC, Department of Contractile Pro- DOUGLAS, WILLIAM B., JR., Department of teins, Institute for Muscle Disease, Inc., Physiology, Michigan State University, East New York. Lansing. GAUTHIER, GERALDINE, Laboratory of Electron DOW, JOCELYN W., MRC Laboratory of Molecular Microscopy, Wellesley College, Wellesley, Biology, Cambridge, England. Mass. DRABIKOWSKI, WITOLD, Department of Bio- GERGELY, JOHN, Department of Muscle Research, chemistry of Nervous Systems and Muscles, Boston Biomedical Research Institute, Boston. Nencki Institute of Experimental Biology, GIAMBALVO,ANTHONY, Department of Biophysics, Warsaw, Poland. State University of New York, Brooklyn. DREIZEN, PAUL, State University of New York, GIBnONS, IAN R., Pacific Biomedical Research Downstate Medical Center, Brooklyn. Center, University of Hawaii, Honolulu. EATON, BARBRA, Biochemistry Graduate Group, GOLDMAN, ROBERT, Department of Biology, Case University of Pennsylvania, Philadelphia. Western Reserve University, Cleveland, Ohio. *EBAsHI, SETSURO, Department of Pharmacology, GOLL, DARREL, Muscle Biology Group, Iowa State Faculty of Medicine, University of Tokyo, University, Ames. Tokyo, Japan. GRANT, ROBERT J., Department of Biological ECKSTEIN, FRITZ, Department of Chemistry, Sciences, Hunter College, New York. Max-Planck-Institut, Gottingen, Germany. GREASER, MARION, Muscle Biology Laboratory, EDWARDS, CttARLES, Department of Biological University of Wisconsin, Madison. Sciences, State University of New York, *HANsoN, JEAN, MRC Biophysics Unit, King's Albany. College, London, England. EISENBERC., BUE~DA, Department of Physiology, HARRINGTON, WILLIAMF., Department of Biology, University of California School of Medicine, Johns Hopkins University, Baltimore. Los Angeles. HARTSHORNE, DAVID J., Department of Chemistry EISENBERG, EVAN, National Heart and Lung and Biological Sciences, Carnegie Mellon Institute, NIH, Bethesda, Md. University, Pittsburgh. EISENBERG, ROBERT, Department of Physiology, HASELGROVE,JOHN, MRC Laboratory of Molecular University of California School of Medicine, Biology, Cambridge, England. Los Angeles. HERMAN, LAWRENCE, Department of Pathology, ELFVIN, MYRA, Department of Anatomy, Medical State University of New York, Downstate College of Pennsylvania, Philadelphia. Medical Center, Brooklyn. ELLIOTT, GERALD F., Department of Physics, HEUMANN, HANs-G~NTHER, Department of Zo- The Open University, Bletchley, England. ology, Lehrstuhl ffir Zellenlehre, Heidelberg, ELZINGA, MARSHALL, Boston Biomedical Research Germany. Institute, Boston. HEYWOOD, STUART, Department of Biology, ENDO, MAKOTO,Department of Biological Sciences, University of Connecticut, Storrs. Purdue University, Lafayette, Ind. HITCHCOCK, SARAH E., Department of Biology, EPPENBERGER, HANS M., Laboratory of Develop- Brandeis University, Waltham, Mass. mental Biology, Swiss Federal Institute of *HOLMES, KENNETH C., Department of Biophysics, Technology, Zurich, Switzerland. Max-Planck-Institut, Heidelberg, Germany. ETLINGER, JOSEPH, Department of Biophysics, HOLT, JOHN C., Department of Structural Biology, University of Chicago, Chicago. Children's Cancer Research Foundation, Bos- FAY, FREDRIC S., Department of Physiology, ton. University of Massachusetts Medical School, HOLTZER, HOWARD, Department of Anatomy, Worcester. University of Pennsylvania School of Medicine, FEIT, THEODORE S., Department of Physiology, Philadelphia. Einstein College of Medicine, Bronx, New HOMSHER, EARL, Department of Physiology, York. University of California Medical Center, Los *Denotes Chairman Angeles. SYMPOSIUM PARTICIPANTS vii

*HUXLEY, ANDREW F., Department of Physiology, LYMN, RICHARDW., MRC Laboratory of Molecular University College, London, England. Biology, Cambridge, England. *HUXLEY, HUGH E., MRC Laboratory of Molecular MAcLENNAN, DAVID H., Banting and Best Depart- Biology, Cambridge, England. ment of Medical Research, University of IKEMOTO, NORIAKI, Department of Muscle Re- Toronto, Toronto, Canada. search, Boston Biomedical Research Institute, MAXINOSE, MADO~A, Department of Physiology, Boston. Max-Planck-Institut, Heidelberg, Germany. JACOBSON, DAVID, McArdle Laboratory, University MALIK, MAZttAR N., Department of Biochemistry, of Wisconsin, Madison. State University of New York, Downstate JOHNSON, JA~ P., Laboratory of Structural Molec- Medical Center, Brooklyn. ular Biology, Children's Cancer Research MANN~ERZ, HANS G., Department of Biophysics, Foundation, Boston. Max-Planck-Institut, Heidelberg, Germany. JOROENSON, ANI~ELISA, Department of Biology, MARCHAND, JOHN F., Department of Clinical University of Connecticut, Storrs. Investigations, Institute for Muscle Disease, JULIAN, FRED, Boston Biomedical Research Insti- Inc., New York. tute, Boston. MAROOSSIAN, SARKIS S, Department of Structural KALDOR, GEORGE, Department of Physiology, Biology, Children's Cancer Research Founda- Medical College of Pennsylvania, Philadelphia. tion, Boston. KAMINER, BENJAMIN, Department of Physiology, MARTONOSI, ANTHONY, Department of Biochem- Boston University School of Medicine, Boston. istry, St. Louis University School of Medicine, KASSLER, HELENE, Department of Biology, Clark St. Louis. University, Worcester, Mass. MATACIC, SLAVICA SMIT, Department of Biology, KATZEFF, HARVEY, Department of Biophysics, Haverford College, Haverford, Penn. State University of New York, Brooklyn. MENDELSON, ROBERT, Cardiovascular Research KAY, CYRIL M., Department of Biochemistry, Institute, University of California, San Fran- University of Alberta, Edmonton, Canada. cisco. KENDRICK-Jo~ES, JOHN, MRC Laboratory of *MILLER, ANDREW, Department of Zoology, Ox- Molecular Biology, Cambridge, England. ford University, Oxford, England. KING, MURRAY V., Laboratory of Physical Bio- MILLER, RICHARD, Department of Biophysics and chemistry, Massachusetts General Hospital, Medicine, State University of New York, Boston. Brooklyn. KOMINZ, DAVID R., Laboratory of Biophysical MOMMAERTS, WILFRIED F. M. M., Department of Chemistry, NIAMD, NIH, Bethesda, Md. Physiology, University of California Medical KUSHMERICK, MARTIN J., Department of Physiol- Center, Los Angeles. ogy, Harvard Medical School, Boston. Moos, CARL, Department of Biochemistry, State LAMVIK, MICHAEL K., Enrico Fermi Institute and University of New York, Stony Brook. Department of Biophysics, University of MORALES, Manuel F., Cardiovascular Research Chicago, Chicago. Institute, University of California, San Fran- LANSMA~, STEVEN, Department of Medicine and cisco. Program in Biophysics, State University of MORRIS, GLENN, Department of Biology, Univer- New York, Brooklyn. sity of Connecticut, Storrs. LEHMAN, WILLIAM, Department of Biology, Bran- MOWERY, PATRICK, Cardiovascular Research In- deis University, Waltham, Mass. stitute, University of California Medical LE~RER, SHERWIN,Department of Muscle Research, School, San Francisco. Boston Biomedical Research Institute, Boston. MURRAY, JOHN, Department of Biochemistry, St. LEVINE, RHEA J., Department of Anatomy, Louis University School of Medicine, St. Louis. Medical College of Pennsylvania, Philadelphia. NACHMIAS, V. T., Haverford College, Haverford, LEVY, RONNIE, Department of Physiology, Har- Penn. vard Medical School, Boston. NAGY, BELA, Department of Muscle Research, LIOItT, SUSAN, Department of Biology, Clark Boston Biomedical Research Institute, Boston. University, Worcester, Mass. NAUSS, KATttLEEN M., Laboratory of Structural LoEwY, ARIEL G., Department of Biology, and Molecular Biology, Children's Cancer Haverford College, Haverford, Penn. Research Foundation, Boston. LOWEY, SUSAN, Children's Cancer Research Foun- NOLA~, A. C., Laboratory of Physical Biology, dation, Boston. NIH, Bethesda, Md. *LowY, Jack, Biophysics Institute, Aarhus Univer- OFFER, G. W., Department of Biophysics, King's sity, Aarhus, Denmark. College, London, England. viii SYMPOSIUM PARTICIPANTS

O'HARA, DONALD, Department of Physiology, Research, Boston Biomedical Research Insti- Massachusetts General Hospital, Boston. tute, Boston. *OosAWA, FUMIO, Institute of Molecular Biology, SCHAE~'FER, SUSAN F., Laboratory of Electron Nagoya University, Nagoya, Japan. Microscopy, Wellesley College, Wellesley, PAUL, RICHARD J., Department of Physiology, Mass. Harvard Medical School, Boston. SC~ZAUB, MARCUS C., Institute of Pharmacology, PEAClfEY, LEE D., Department of Biology, University of Switzerland, Zurich. University of Pennsylvania, Philadelphia. SCIIEIN, STANLEY J., Department of Molecular PEMRICK, SUZANNE M., Department of Biological Biology, Einstein College of Medicine, Bronx, Sciences, State University of New York, New York. Albany. SCHLISEI,FELD, LOUIS H., Department of Contract- PEPE, FRANK A., Department of Anatomy, ile Proteins, Institute for Muscle Disease, Inc., University of Pennsylvania School of Medicine, New York. Philadelphia. SCHOENBERG, MARK, Laboratory of Physical *PERRY, S. V., Department of Biochemistry, Biology, NIAMD, NIH, Bethesda, Md. University of Birmingham, Birmingham, Eng- SCORDILIS,STYLIANOS P., Department of Biological land. Sciences, State University of New York, PODOLSKY, RICH.r J., National Institute of Albany. Arthritis and Metabolic Diseases, NIH, Beth- SEIDEL, JOHN, Department of Muscle Research, esda, Md. Boston Biomedical Research Institute, POLLARD, TtIOMAS D., National Heart and Lung Boston. Institute, NIH, Bethesda, Md. SHAH.',', EZRA, Department of Biological Science, POTTER, JAMES D., Department of Muscle Research, Hunter College, New York. Boston Biomedical Research Institute, Boston. SIEMANKOWSKI, RAYMOND, Department of Med- PULLMAN, JAMES M., Department of Biophysics, icine and Program in Biophysics, State University of Chicago, Chicago. University of New York, Brooklyn. REEDY, MICHAEL K., Department of Anatomy, SIMS, JOH.',- M., Department of Physiology and Cell Duke University, Durham, N.C. Biology, University of Kansas, Lawrence. REGE.~,~STEIN, JOE M., Department of Biophysics, SMALL, J. V., Biophysics Institute, Aarhus Univer- Brandeis University, Waltham, Mass. sity, Aarhus, Denmark. REISLER, EMIL, Department of Biology, Johns SMILLIE, L. B., Department of Biochemistry, Hopkins University, Baltimore. University of Birmingham, Birmingham, Eng- RICE, ROBERT V., Department of Biological land. Sciences, Carnegie Mellon University, Pitts- SORENSON, MARTIIAM., Department of Neurology, burgh. College of Physicians and Surgeons, New York. RICHARDS, DE.'~'IS, Department of Medicine and SPUDICH, JAMES A., Department of Biochemistry Program in Biophysics, State University of and Biophysics, University of California, New York, Brooklyn. San Francisco. RICHARDS, E. GLEN, Department of General Med- SPURWAY, N. C., Department of Biology, Univer- ical Research, Veterans Administration Hos- sity of Pennsylvania, Philadelphia. pital, Dallas. STEIGER, G. J., Department of Cell Physiology, ROME, ELIZABETH, MRC Muscle Biophysics Unit, Ruhr University, Bochum, Germany. King's College, London, England. STOCK, GREGORY B., Department of Biophysics, SABBADINI, ROGER A., Department of Zoology, Johns Hopkins University, Baltimore. University of California, Davis. STONE, DEBORAH B., Cardiovascular Research SAIDE, JUDITH, Department of Physics and Institute, University of California, San Fran- Biochemistry, Massachusetts General Hospital, cisco. Boston. STRACHER, ALFRED, Department of Biochemistry, SANDOW, ALEXANDER, Department of Physiology, State University of New York, Downstate Institute for Muscle Disease, Inc., New York. Medical Center, Brooklyn. SA~'GER, JOSEPI[ W., Department of Anatomy, STULL, JAMES T., JR., Department of Biological University of Pennsylvania School of Medicine, Chemistry, University of California School of Philadelphia. Medicine, Davis. SANTERRE, ROBERT, Department of Biology, SZENT-GYoRGYI, ALBERT, Marine Biological Labor- Massachusetts Institute of Technology, Cam- atory, Woods Hole, Mass. bridge. SZENT-GY('JRGYI, ANDREW, Department of Biology, SxaKXa, SATYAPRIYA, Department of Muscle Brandeis University, Waltham, Mass. SYMPOSIUM PARTICIPANTS ix

SZENT-GYoR(]YI, EVE, Department of Biology, WACHSBERGER, PHYLLIS,Department of Anatomy, Brandeis University, Waltham, Mass. University of Pennsylvania School of Medi- TADA, MICHIHIKO,Department of Cardiology, Mr. cine, Philadelphia. Sinai School of Medicine, New York. *WEBER, ANNEMARIE, Department of Biochem- TAM, DOMINIC, Department of Biophysics and istry, St. Louis University School of Medicine, Medicine. State University of New York, St. Louis. Brooklyn. WEEDS, A. G., MRC Laboratory of Molecular TAYLOR, DOUGLASS L., Department of Biology, Biology, Cambridge, England. State University of New York, Albany. WEISEL, JOHN W., Department of Biophysics, TAYLOR, EDWIN W., Department of Biophysics, Brandeis University, Waltham, Mass. University of Chicago, Chicago. WHITE, DAVID C. S., Department of Biology, THOMPSON, WILLIAM C., Department of Genetics University of York, York, England. and Cell Biology, University of Connecticut, WIENER, STANLEY L., Department of Medical Storrs. Research, Long Island Jewish Medical Center, TONOMURA, YCJI, Department of Biology, Faculty New Hyde Park, New York. of Science, Osaka University, Osaka, Japan. *WILKIE, D. R., Department of Physiology, *TREGEAR, RICHAI~D T., Department of Zoology, University College, London, England. University of Oxford, Oxford, England. WOLEDGE, ROGEa C., Department of Physiology, TRENTHAM, D. R., Department of Biochemistry, University College, London, England. University of Bristol School of Medicine, YAFFE, DAVID, Department of Biology, Massa- Bristol, England. chusetts Institute of Technology, Cambridge. TWAROG, BETTY M., Department of Biology, YOUNG, MICHAEL,Department of Medicine, Massa- Tufts University, Medford, Mass. chusetts General Hospital, Boston. VIBERT, PETER J., Biophysics Institute, Aarhus YOUNT, RALPH G., Department of Chemistry, University, Aarhus, Denmark. Washington State University, Pullman. Albert Szent-Gy6rgyi Opening Remarks First row: S. V. Perry - - It. E. Huxley, S. Ebashi - - E. Eisenberg. Second row: D. R. Trentham - - F. Oosawa, N. A. BirS, S. Ebashi - - L. H. Schliselfeld. Third row: R. S. Adelstein-- R. J. Podolsky-- M., K., and G. B~rs ~b ....

First row: N. h. Bir6 - - R. W. Lymn, J. Hanson - -W. F. Harrington. Second row: L. D. Peachey - - M. Elzinga - - R. V. Rice, D. Bray. Third row: E. Shahn -- J. Haselgrove-- H. Carney. First row: C. Moos - - A. Miller - - W. F. M. M. Mommaerts. Second row: P. Dreizen -- T. Pollard, A. F. Huxley-- S. Lowey, A. Miller, S. Sarkar. Third row: M. Young - - S. E. Hitchcock, R. T. Tregear - - R. G. Yount. Fourth row: F. A. Pepe, E. Gaetjens - - J. V. Small, S. Heywood, G. Morris --J. Gergely. ~ ? ~i~ 84 ~i!!~:i~:i~i:~i!~:~~iii'~'~~'~ ~:~ii'~i:i~ ~

~ ~~ ~'~'"~'ii ii~iiii~iiiiill !ii~!~84 ;~ ~ ::~i ~ ~ i!ii~ii~ Foreword

Our symposium each year gives us the opportunity to seek an exploding phase of biology and to bring together most of the key practitioners. With the emergence of the sliding filament model the field of muscle contraction has become in itself a major intellectual discipline, with its own well-defined objectives. On no occasion, however, since the sliding filament model was first presented has it been possible to bring together all the many people whose research directly bears on the molecular events underlying the contraction process. So it seemed most appropriate to devote this year's symposium to this theme. In preparing this program, I greatly profited from the advice of Carolyn Cohen, John Gergely, Andrew Huxley, Hugh Huxley, and Andrew Szent-GySrgyi. They suggested many more speakers than we could accommodate even in a very full week's program. So, regretfully, we were not able to include on the final program everyone who had something important to say. But, hopefully, the high level of animated discussion that occurred throughout the week allowed us to hear about all new facts of importance. It is our belief that this symposium volume will be of great value, not only in telling us about the current state of muscle research, but also in pointing out what problems remain to be solved. Fortunately we were able to entice Albert Szent-GySrgyi to open the program, thereby allowing us again to appreciate his vast contributions to the way we think about contraction. During the succeeding seven days, the formal program sessions were generally held in the mornings and evenings, with the afternoons reserved for more informal gatherings. The meeting ran from the evening of June 6th to noon on June 13th. Approxi- mately 210 people were in attendance. As in the past, the program was supported by the National Institutes of Health, the National Science Foundation, and the United States Atomic Energy Commission. In charge of putting together the resulting volume has been Judy Gordon, who served as managing editor, ably assisted by Mary Lewis and Kate Alston.

James D. Watson Director

xvii Contents

Symposium Participants vii Foreword xvii

SEQUENCE, SUBUNITS, AND ASSEMBLY OF MUSCLE PROTEINS

The Amino Acid Sequence of Rabbit Skeletal Muscle Aetin M. Elzinga and J. H. Collins 1 Structural Studies on the Light Chains of Myosin A.G. Weeds and G. Frank 9 Stoichiometry and Sequential Removal of the Light Chains of Myosin S. Sarkar 14 A Phosphorylated Light Chain Component of Myosin from Skeletal Muscle W. T. Perrie, L. B. Smillie, and S. V. Perry 17 An Immunochemieal Approach to the Interaction of Light and Heavy Chains in Myosin S. Lowey and J. C. Holt 19 Studies on the Role of Light and Heavy Chains in Myosin Adenosine Triphos- phatase P. Dreizen and D. H. Richards 29 Myosin-linked Regulatory Systems: The Role of the Light Chains J. Kendrick- Jones, E. M. Szentkirdlyi, and A. G. Szent-GySrgyi 47 Studies on the Helical Segment of the Myosin Molecule N.A. Bir6, L. Szilagyi, and M. Bdlint 55 Studies on the Structure and Assembly Pattern of the Light Meromyosin Section of the Myosin Rod M. Young, M. V, King, D. S. O'Hara, and P. J. Molberg 65 Association of Myosin to Form Contractile Systems W. F. Harrington, M. Burke, and J. S. Barton 77 C-Protein and the Periodicity in the Thick Filaments of Vertebrate Skeletal Muscle G. Offer 87 The Myosin Filament: Immunochemieal and Ultrastructural Approaches to Molecular Organization F. A. Pepe 97 Filaments from Purified Smooth Muscle Myosin A. Sobieszek and J. V. Small 109

ATPASE AND CONTRACTION

Inhibition of Heavy Meromyosin by Purine Disulfide Analogs of Adenosine Triphosphate R. G. Yount, J. S. Frye, and K. R. O'Keefe 113 Inhibition of Myosin ATPase with a Disulfide Analog of ATP H.J. Mannherz, R. S. Goody, and F. Eckstein 119 An ATP-Binding Peptide G. Barany and R. B. Merrifield 121

xix xx CONTENTS

Transient Kinetic Studies of the Mg++-dependent ATPase of Myosin and Its Proteolytic Subfragments C. R. Bagshaw, J. F. Eccleston, D. R. Trentham, D. W. Yates, and R. S. Goody 127 Actin Activation of Heavy Meromyosin and Subfragment-1 ATPases: Steady State Kinetics Studies C. Moos 137 Evidence for a Refractory State of Heavy Meromyosin and Subfragment-1 Unable to Bind to Actin in the Presence of ATP E. Eisenberg and W. W. Kielley 145 Possible Differentiation between Rigor Type Interactions of the Two Myosin Heads with Actin M. C. Schaub and J. G. Watterson 153 A Proposal for the Mechanism of Contraction in Intact Frog Muscle M. Bdrdny and K. Bdrdny 157 Formation and Decomposition of the Myosin-Phosphate-ADP Complex in the Myosin-ATPase Reaction Y. Tonomura, Y. Hayashi, and A. Inoue 169 Studies on the Mechanism of Myosin and Actomyosin ATPase J. F. Koretz, T. Hunt, and E. W. Taylor 179 Investigation of Conformational Changes in Spin-labeled Myosin: Implications for the Molecular Mechanism of Muscle Contraction J. C. Seidel and J. Gergely 187 Does A Myosin Cross-Bridge Progress Arm-over-Arm on the Actin Filament? J. Botts, R. Cooke, C. dos Remedios, J. Duke, R. Mendelson, M. F. Morales, T. Tokiwa, G. Viniegra, and R. Yount 195 Links between Mechanical and Biochemical Kinetics of Muscle D.C.S. White 201

MUSCLE REGULATORY SYSTEMS

Regulatory Proteins of Muscle with Special Reference to Troponin S. Ebashi, I. Ohtsuki, and K. Mihashi 215 Studies on the Subunit Composition of Troponin D.J. Hartshorne and P. Dreizen 225 Troponin Subunits and Their Interactions M. L. Greaser, M. Yamaguchi, C. Brekke, J. Potter, and J. Gergely 235 Troponin--Its Composition and Interaction with Tropomyosin and F-Actin W. Drabikowski, E. Nowak, B. Barylko, and R. Dabrowska 245 Localization and Mode of Action of the Inhibitory Protein Component of the Troponin Complex S. V. Perry, H. A. Cole, J. F. Head, and F. J. Wilson 251 I Phosphorylation and Dephosphorylation of the Inhibitory Component of Troponin J. T. Stull, P. J. England, C. O. Brostrom, and E. G. Krebs 263 Manifestations of Cooperative Behavior in the Regulated Actin Filament during Actin-activated ATP Hydrolysis in the Presence of Calcium R.D. Bremel, J. M. Murray, and A. Weber 267 Dynamic Property of F-Actin and Thin Filament F. Oosawa, S. Fujime, S. Ishiwata, and K. Mihashi 277 Tropomyosin-Troponin Assembly C. Cohen, D. L. D. Caspar, J. P. Johnson, K. Nauss, S. S. Margossian, and D. A. D. Parry 287 Tropomyosin: Amino Acid Sequence and Coiled-Coil Structure R.S. Hodges, J. Sodek, L. B. Smillie, and L. Jurasek 299 Structure of the Actin-containing Filaments in Vertebrate Skeletal Muscle J. Hanson, V. Lednev, E. J. O'Brien, and P. M. Bennett 311 Myosin-linked Regulatory Systems: Comparative Studies W. Lehman, J. Kendrick-Jones, and A. G. Szent-Gy6rgyi 319

MUSCLE STRUCTURE Structural Studies by X-Ray Diffraction of Striated Muscle Permeated with Certain Ions and Proteins E. Rome 331 CONTENTS xxi

X-Ray Evidence for a Conformational Change in the Actin-containing Filaments of Vertebrate Striated Muscle J. C. Haselgrove 341 Studies of the Low-Angle X-Ray Pattern of a Mulluscan Smooth Muscle during Tonic Contraction and Rigor J. Lowy and P. J. Vibert 353 Structural Changes in the Actin- and Myosin-containing Filaments during Contraction H. E. Huxley 361 Changes in the Polarization of Tryptophan Fluorescence in the Actomyosin System of Working Muscle Fibers G. J. Steiger, J. C. Riiegg, K. M. Boldt, D. W. Liibbers, and W. Breull 377 The Structure and Function of Insect Muscle P. Armitage, A. Miller, C. D. Rodger, and R. T. Tregear 379 Intensity Fluctuation Autocorrelation Studies of Resting and Contracting Frog Sartorius Muscle F. D. Carlson, R. Bonner, and A. Fraser 389 How Many Myosins per Cross-Bridge? I. Flight Muscle Myofibrils from the Blowfly, Sarcophaga buUata M. K. Reedy, G. F. Bahr, and D. A. Fischman 397 How Many Myosins per Cross-Bridge? IX. Flight Muscle Myosin from the Blowfly, Sarcophaga bullata B. Bullard and M. K. Reedy 423 Biochemical and Ultrastructural Studies on Vertebrate Smooth Muscle R.V. Rice and A. C. Brady 429 The Core Component of the Myosin-containing Elements of Vertebrate Smooth Muscle J. V. Small and A. Sobieszek 439 Effects of ATP Analogs on the Low-Angle X-Ray Diffraction Pattern of Insect Flight Muscle J. Barrington Leigh, K. C. Holmes, H. G. Mannherz, G. Rosenbaum, F. Eclcstein, and R. Goody 443 X-Ray Diagrams from Skeletal Muscle in the Presence of ATP Analogs R.W. Lymn and H. E. Huxley 449 SARCOPLASMIC RETICULUM

The Biosynthesis of Sarcoplasmic Reticulum Membranes and the Mechanism of Calcium Transport A. Martonosi, R. Boland, and R. A. Halpin 455 Isolation of Sarcoplasmic Reticulum Proteins D. H. MacLennan, C. C. Yip, G. H. Iles, and P. Seeman 469 Electrical Events in the T-System of Frog Skeletal Muscle L.D. Peachy 479 Calcium and the Control of Contraction and Relaxation in a Molluscan Catch Muscle B. Twarog and Y. Muneoka 489 Length Dependence of Activation of Skinned Muscle Fibers by Calcium M. Endo 505 MYOGENESIS

M and Z Band Components and the Assembly of Myofibrils J. D. Etlinger and D. A. Fischman 511 Functions of Cytoplasmic Fibers in Non-Muscle Cell Motility R. D. Goldman and D. M. Knipe 523 Myosin Messenger RNA : Studies on Its Purification, Properties and Translation during Myogenesis in Culture G. E. Morris, E. A. Buzash, A. W. Rourke, K. Tepperman, W. C. Thompson, and S. M. Heywood 535 Gene Expression during Differentiation of Contractile Muscle Fibers D. Yaffe and H. Dym 543 Selected Topics in Skeletal Myogenesis H. Ho~tzer, J. W. Sanger, H. Ishikawa, and K. Strahs 549

CONTRACTILE PROTEINS IN NON-MUSCLE TISSUE

Cytoplasmic Actin: A Comparative Study D. Bray 567 The "Contractile" Proteins of Acanthamoeba castellanii T. D. Pollard and E. D. Korn 573 xxii CONTENTS

Effects of Cytochalasin B on Actin Filaments J.A. Spudich 585 Studies on the Contractile Proteins from Blood Platelets J. Abramowitz, M. N. Malik, A. Stracher, and T. C. Detwiler 595 The Characterization of Contractile Proteins from Platelets and Fibroblasts R. S. Adelstein and M. A. Conti 599 Physarum Myosin: Two New Properties V.T. Nachmias 607

ENERGETICS AND MECHANICAL PROPERTIES

Heat, Work, and Phosphocreatine Splitting during Muscular Contraction C. Gilbert, K. M. Kretzsehmar, and D. R. Wilkie 613 Chemical and Mechanical Changes during Stretching of Activated Frog Skeletal Muscle N. 'A. Curtin and R. E. Davies 619 Comments on Activation Heat and Its Relation to Activation A. Fraser 627 In Vitro Calorimetric Studies Relating to the Interpretation of Muscle Heat Experiments R. C. Woledge 629 Regulation of Force and Speed of Shortening in Muscle Contraction F.J. Julian and M. R. Sollins 635 An Interpretation of the Effects of Fiber Length and Calcium on the Mechanical Properties of Insect Flight Muscle R.H. Abbott 647 Estimates of Force and Time of Actomyosin Interaction in an Active Muscle and of the Number Interacting at Any One Time J. Pybus and R. Tregear 655 Muscle Contraction Transients, Cross-Bridge Kinetics, and the Fenn Effect R. J. Podolsky and A. C. Nolan 661 Mechanical Transients and the Origin of Muscular Force A. F. Huxley and R. M. Simmons 669 The Conversion of Osmotic into Chemical Energy Coupled with Calcium Trans- location across the Sarcoplasmic Membrane M. Makinose 681 A Model for Muscle Contraction in Which Cross-Bridge Attachment and Force Generation Are Distinct F. J. Julian, K. R. Sollins, and M. R. Sollins 685

Summary

Muscle 1972: Progress and Problems H.E. Huxley 689

Subject Index 695 Name Index 699