I8.6 SecondaryStructure of Proteins 565

Fouow-upro rHECnsr ln Polnr: Runner'shish Karla sometimes experiences runner's high during period of exercise to increase all-around mental alert- her runs. \Alhat is causing this effect? Many sports ness and a sense of comfort. Exercise is a good thiag, physiologists believe that runner's high comes from but like most good things, it can be overdone, since increases in the levels of enkephalins in the brain. the body may suffer from exhaustion and other These increases, which remarkabie feel- breakdornmswhen overtaxed without sufficient time "* "urrr" ings of well-belng, appear to be stimulated by to recover. Enkephalins may be responsrble in part endurance exercises such as distance running. The for the potentially harmful addiction of some people effects of enkephalins appear to last beyond the IO eXCeSStVeexerclse_

18,5Primory structure of proteins AIM: To chorocterizethe primory structureof o protein

INhen the number of amino Focus acid residuesbecomes greater than about 40, a naturally occurringpeptide is called aprotein. On average,a peptide mole- The primary structure is the cule containing 100amino acid residueshas a molar massof about 10,000 first level of organization of a g. Proteins are so vitai to living organisms that many of the remaining top- protein. ics in this book concernthem. The structuresof proteins areusually studied at four levels of organization: primary structlffe, secondarystructure, ter- tiary structure, and quaternary structure. The prirnary structure of a pep- tide or protein is the order in which the residuesof a peptide or protein molecule are linked by peptide bonds. The primary structure of a protein moleculealso includes any disulfidebridges that the molecule con- tains.Iust aswe sawfor peptidesin the precedingsection, differences in the Protein chemicaland biologicalproperties of proteinsresult from differencesin the proteios(Greek): offirst order of amino acidsin the polypeptide chain (primary structure).The sec- importance ondary tertiary and quaternarystructures of proteins are discussedin the following three sections.

18.6Secondory stractare of proteins AIMS: To describethe bonding ond structurein the following secondarystructures of proteins: alpho , beto-pleoted sheet,ond collogenhelix. Todistinguish omong the following fibrous proteins: olpho keratin, beto kerotin, ond .

The polypeptide The alpha heli5 beta-pleated chains of many proteins contain specific,repeating pat- sheet, and collagen helix are terns of folding of the peptide backbone. Thesespecific, repeating patterns three types of secondary struc- of folding of the peptide backboneconstitute the protein'ssecondary struc- tures found in proteins. ture. Three commonly found patterns are the , t]r.ebeta-pleated sheet,andthe collagen helix. 564 CHAPTERl8 Amino Acids,Peptides, and Proteins

Alpha helix In someproteins, regionsof the backboneof the peptide chain are coiled into a shape called an alplaalnelix, similar to a corkscrew.As Figure lB.3 shows, a corkscrew must be turned in a right-handed, or clockwise, direc- tion to penetrate a cork. The alpha of proteins are always right- handed. The helixes are held together by hydrogen bonds, shornmin Figure 18.4,formed between the hydrogen of an N-H of a peptide bond and the carbonyl oxygen of another peptide bond group four residues away in the samepeptide chain. The tightnessof coiling is such that 3.6 amino acid residuesof the pep- tide backbone make each ftrll of the alpha helix. There are no amino acid residue side chains inside the alpha helix; they are located on the out- side. The cyclic amino acid does not fit well into the peptide back- bone of alpha helixes. Alpha helixes in long protein chains often end at a place where proline residues occur in the primary structure. Proline is

Figute18.5 A corkscrewmust be turned in a t right-handed,or clockwise,direc- To N-terminal tion to penetratea cork.

I

Figute18.4 t; A peptide chaintwisted into a right-handedalpha helix constitutes a protein'ssecondary structure. The N-terminalto C-terminaldirection is from top to bottom.The dotted linesshow the hydrogenbonds betweenthe carbonylorygen of one aminoacid residue and the N-H hydrogenof another,four amino acid residuesfurther down the chain. 18.6Secondary Structure of Proteins 565

sometimes called an alpha helix disrupter for this reason. The inability of proline to fit into the alpha helix is one of many piecesof euidencethai the secondarystructure of a protein is determined by its primary structure. Much of what is knolrrn about protein alpha helixes comes from studies of fibrous proteins. Fibrous proteins tend to be long, rod-shaped molecules with great mechanical strength. Such proteins are usually insoluble in water, dilute salt solutions, and other solvents. The polypeptide chains of a class of fibrous proteins called alpha keratins consist mainly of alpha helixes.Alpha keratins form the hard tissue of hooves, horns, outer skin layer (epidermis), hair, wool, and nails of mammals. We see in Figure lB.5 complexprotein molecules consisting of long alpha helixes that are twisted together-supercoiled-in ropes of three or seven strands. It takes many supercoiled ropes to make a strong but elastic wool fiber. If you have ever washed a wool sweater, you know that warm, wet wool fibers can be stretched, but they eventually return to their original length. This is because the alphahelixes of the damp fibers are easilypulled into an extended form. The extended form is less stable than the alpha helix. It will, in time, return (a) Helical peptide (b) Alpha keratin to the original alpha helix. Disulfide bridges (seeSec. lB.1) between alpha chain helixes help to make alpha keratins rigid; the alpha keratins of a hard hoof Figure18.5 have more disulfide linkages than relatively elastic epidermis. Threehelical peptide chains,like the one shown in (a), are twisted Beta-pleated sheet or supercoiledto form a rope in alpha keratin(b). Figure l8.6 showsthe beta-pleatedsheet, another kind of secondarystruc- ture commonly found in proteins. Thebeta-pleated sheet consistsof pep- tide chains arranged side by side to form a structure that resemblesa pieceof paper folded into many pleats. The carbonyl groups of one zigzagpeptide backbone are hydrogen bonded to peptide N-H hydrogens of adjacent peptide chains that run in opposite directions in the N-terminal to C-ter-

Figure18.6 A beta-pleatedsheet is another kindof secondarystructure. Hydro- C-terminal genbonds (shown as dotted lines) holdadjacent strands of the sheet together.

t-= N-terminal ':a:--

-a.

@ carbon @ o*yg"n ;g Hydrogen

@ uirrog".r $ sidectrain I Hydrogenbond 566 CHAPTERl8 Amino Acids,Peptides, and Proteins

.;- Figure18.8 .J Silkfibroin consists of stackedbeta-pleated l'_' sheets.The small R ::: groupsof glycyland alanylresidues permit the stacking to occur.

minal sense.Beta-pleated sheets are formed by separatestrands of protein or by a single chain looping back on itself. Figure18.7 Beta keratin s are a classof fibrous proteins that consist mainly of beta- Spiderwebs aremade of fibroin,a pleated sheets.The long, thin fibers secretedby silkworms and spiders (Fig' proteinthat existsmainly as beta- 18.7)are composedof fibroin, a well-studied beta keratin. Fibroin consists pleatedsheets. mainly of layersof beta-pleatedsheets, as shornrnin Figure lB.B.Again, the primary structure of a protein determinesits secondarystructure. Fibroin peptide chains are particularly rich in glycyl and alanyl residues.The small side chains of these residuesare important to the organization of fibroin, since larger side chains would interfere with the packing of the sheetsin layers.

Collagen helix Collagenis yet another kind of fibrous protein. Collagen is the most abun- dant protein in human beingsand many otheranimals with spinal columns (uertebrates).About one-third of the protein in the human body is present as the collagenof bones,teeth, inner skin layer (dermis),tendons, and car- tilage.The inner material of the eye lens is almost pure collagen.Collagen occurs in all organs,where it imparts strength and stiffness. Collagenis formed from three peptide chains,each a helix,wound into a rope.There are important differencesbetween alpha helixesand collagen helixes,however. Collagen is rich in proline (40To),which does not fit into regular alpha helixes, and collagen helixes are not as tightly coiled as alpha helixes. Unlike alpha helixes, which are right-handed, collagen helixes are left-handed. Collagen contains large quantities of (35%)and the unusual amino acids4-hydroxlproline (5%)and S-hydroxylysine(1%). OH I H9-9u, tt cHr. .cH-co2H ?' T"' N H2N-CH2-CH-CH2 -C"r-f -n I H co2H 4- 5-Hydroxylysine