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The New Architectonics: an Invitation to Structural Biology

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The New Architectonics: an Invitation to Structural Biology THE ANATOMICAL RECORD (NEW ANAT.) 261:198–216, 2000 FEATURE ARTICLE The New Architectonics: An Invitation To Structural Biology CLARENCE E. SCHUTT* AND UNO LINDBERG The philosophy of art might offer an epistemological basis for talking about the complexity of biological molecules in a meaningful way. The analysis of artistic compositions requires the resolution of intrinsic tensions between disparate sensory categories—color, line and form—not unlike those encountered in looking at the surfaces of protein molecules, where charge, polarity, hydrophobicity, and shape compete for our attentions. Complex living systems exhibit behaviors such as contraction waves moving along muscle fibers, or shivers passing through the growth cones of migrating neurons, that are easy to describe with common words, but difficult to explain in terms of the language of chemistry. The problem follows from a lack of everyday experience with processes that move towards equilibrium by switching between crystalline order and chain-like disorder, a commonplace occurrence in the submicroscopic world of proteins. Since most of what is understood about protein function comes from studies of isolated macromolecules in solution, a serious gap exists between what we know and what we would like to know about organized biological systems. Closing this gap can be achieved by recognizing that protein molecules reside in gradients of Gibbs free energy, where local forces and movements can be large compared with Brownian motion. Architectonics, a term borrowed from the philosophical literature, symbolizes the eventual union of the structure of theories—how our minds construct the world—with the theory of structures—or how stability is maintained in the chaotic world of microsystems. Anat Rec (New Anat) 261:198–216, 2000. © 2000 Wiley-Liss, Inc. KEY WORDS: architectonics; cytoskeleton; functional microanatomy; molecular motor; structural biology; proteins; hydrophobic effect; Gibb’s free energy; thermodynamics; proteomics REDUCTIONISM IN THE plausible case could be made that they ment—will soon be freely available to POST-GENOMIC ERA didn’t exist at all, and even if they did, everyone to probe, exploit, or to study it wasn’t clear how mere aggregations as new form of knowledge about our- We are coming to grips with our mo- could give rise to distinct qualities selves. While it is not at all obvious lecular destiny. Just one hundred (Duhem, 1914). The application of x- how we will read this map, it is a years ago, when it appeared impossi- ray analysis to crystals by Max von certainty that a sound understanding ble that atoms could ever be seen, a Laue, William Bragg, Sr. and Jr., of the structure of proteins will be changed all of that in short order. needed, because all of life’s in- Dr. Lindberg is Professor of Zoological Their legacy, delivered by subsequent termeshed processes, including the Biology at the Wenner-Gren Institute of Stockholm University. He is First Vice- generations of x-ray crystallogra- natural decoding of the message, act President and Foreign Secretary of The phers, is that structures of complex through them. Royal Swedish Academy of Sciences, and Past Chair of the Stockholm branch of the biological macromolecules, whose We are now accustomed to hearing Swedish Folk University. Dr. Schutt is presence was barely suspected a cen- about “the post-genomics era” and Professor of Chemistry at Princeton Uni- versity. He is a Member of the Program in tury ago, can not only be seen, but words like “proteomics” and “emer- Neuroscience, an Associated Faculty obey the ordinary laws of physical gomics” are meant to alert us to where Member in the Molecular Biology Depart- ment, and former Director of the Molecu- chemistry. Genes themselves, a math- the real intellectual or technological lar Biophysics Program. He is Chairman ematical abstraction needed to ex- (not to say investment) opportunities of the Board of the National Alliance for plain regularities in plant heredity, lie. The “proteome” is the set of all Autism Research and Annual Co-Chair and Founder of the Princeton-Eden Lec- were revealed as elaborate three-di- proteins actually present in a given ture Series on Autism. mensional structures containing nu- cell, as revealed by electrophoresis *Correspondence to: Clarence E. Schutt, The Henry H. Hoyt Laboratory, Wash- cleic acids wrapped around proteins. gels capable of resolving thousands of ington Road, Princeton University, The human genome—nothing less distinct spots, each reporting the pres- Princeton, NJ, 08544, USA. E-mail: [email protected] than a highly encoded map of our ma- ence of a single protein. Similarly, terial being, its history and develop- patterns of gene expression, both spa- © 2000 Wiley-Liss, Inc. FEATURE ARTICLE THE ANATOMICAL RECORD (NEW ANAT.) 199 tially and temporally, can be found by to the complexity of speakable ideas. teins (see Figure 2) . These surfaces expanding the repertoire of messen- An idea that contains too many are somewhat easier to describe be- ger RNA present in individual cells minute yet closely related parts, too cause they are shaped to conform to and identifying them with antibodies many relations within relations, can- one another. Even though each is or anti-sense oligomers of DNA. The not be ‘projected’ onto discursive complicated in itself, the pleasing amount of information will be stag- forms; it is too subtle for speech.“ “clasped hands” nature of their mu- gering and its implications for under- Langer (1967) is claiming that the tual interactions, allows us to grasp standing human diseases and affect- boundary conditions set by the linear the meaning of the functional associ- ing cures can be hardly exaggerated. structure of sentences limits what we ation. As one becomes familiar with All of this appears to represent the can communicate about the arts different classes of interactions and triumph of reductionism; all compo- through language alone. The great motifs by studying many crystal struc- nents and sub-components of living works of art must speak for them- tures, a kind of visual gallery develops, systems can be described, in princi- selves directly through the multiple which can form the basis for a lan- ple, by atomic structures. Atoms com- portals of our senses to some con- guage having its own syntax and se- bine to form molecules, some of them sciousness beyond words. mantic rules. To participate in the dis- very large indeed, such as proteins, In many ways, the surfaces of pro- courses of structural biology, one which require for their synthesis min- teins share this discursive aspect with must learn how to express what one iature machine-like ribosomes. Pro- the visual arts (see Figures 1 and 2). It means to say about biological func- teins are synthesized as long chains, is difficult to find words to describe tion in this language. annealing into compact structures in the complexity of form one sees. One It is this aspect of structural biology tiny oven-like chambers called chap- that invites comparison with formal eronins. Recently, the structures of criticism in the arts or in literature. some of the chaperonins (Sigler et al., Architectonics pertains When an art critic assesses a new 1998), and even the ribosome itself work, he or she assumes that the (Wimberly et al., 2000; Ban et al., to both “the theory of reader knows something of the history 2000), have yielded their secrets to structure,” as in the of art. To see the new demands knowl- crystallographers, now armed with edge of the old. But there is more to it. powerful synchrotron x-ray sources, architectural literature, References to earlier works carry with and computers with awesome capa- and “the structure of them contexts of discovery, break- bilities for data reduction and visual- through and failure, drawing from the ization. These structures show us the theory,” used by reader’s consciousness a broad spec- arrangement of the working parts and philosophers to denote trum of memories and feelings. It is set the stage for understanding how the intention of the critic to set the these movements are coordinated to the processes by which stage for these evoked responses. The carry out the functions of these com- ideas become fixed in mind then becomes receptive to the plex particles. our consciousness. critic’s message. In structural biology, certain structures are “classic” in the same way that the paintings of Ce- WHAT IS ARCHITECTONICS? zanne, Van Gogh, Picasso, Rothko, or Architectonics is a venerable term in is clearly in the presence of a compo- Stella define unique compositional the philosophical literature. It per- sition, but even the canonical forms of styles, immediately recognizable, tains to both “the theory of structure”, sculpture, including Alexander Calder’s evocative. We will refer to these clas- as in the architectural literature, and mobiles, are inadequate to the task of sic structures as “structural para- “the structure of theory”, used by phi- describing all of the events that take digms.” losophers in a variety of ways to de- place during protein folding or during But, architectonics is not the same note the processes by which ideas be- the encounter of two proteins. Even if as architecture; “tonics” refers to ten- come fixed in our consciousness the surfaces are color-coded for sions inherent in a structure. Return- (Kant, 1787). Suzanne K. Langer charge, hydrophobicity, and polarity, ing to Langer’s analysis of artistic (1967) in her magisterial three-vol- the presence of ridges, clefts, knobs, composition: “The most fundamental ume work on the philosophy of art and holes adds so much texture and elements seem to be tensions; and uses the word “architectonics” to ex- landscape to the chemical complexity upon closer inspection, tensions show pound on the discursive, non-sequen- that one is at a loss for where to begin.
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