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This regular structure allows thechains to wind around one another to generate a long regular triple helix (Figure3-27A). Many collagen molecules then bind to one another side-by-side andend-to-end to create long overlapping arrays-thereby generating the extremelytough collagen fibrils that give connective tissues their tensile strength, asdescribed in Chapter 19.ManyProteinsContaina SurprisinglyLargeAmountofUnstructuredPolypeptideChainIt has been well kno',.tmfor a long time that, in complete contrast to collagen,another abundant protein in the extracellular matrix, elastin, is formed as ahighly disordered pollpeptide. This disorder is essentialfor elastin'sfunction. ItsFigure3-27 Collagenand elastin.(A)Collagenis a triplehelixformedbythreeextendedproteinchainsthat wraparound one another(bottom).Manyrodlikecollagenmoleculesarecrosslinkedtogetherin the extracellularspaceto form unextendablecollagenfibrils(top)that havethe tensilestrengthofsteel.Thestripingon the collagenfibriliscausedby the regularrepeatingarrangementof the collagenmoleculeswithinthe fibril.(B)Elastinpolypeptidechainsarecross-linkedtogetherto formrubberlike,elasticfibers.Eachelastinmoleculeuncoilsinto a moreextendedconformationwhen the fiber is stretchedand recoilsspontaneouslyas soonasthestretchingforceis relaxed.elasticfiber-short sectionof-collagenfibrilcoilagenmolecule3 0 0n m x 1 .
5n mSTRETCHTi5nmI(A)c o ll a g e ntriplehelixs i n g l ee l a s t i nm o l e c u l ei, :pROTEINS.THESHApEAND STRUCTUfiE,OF, 'l,,',,,.,',,',:. 147relatively loose and unstructured poll,?eptide chains are covalently cross-linkedto produce a rubberlike elastic meshwork that can be reversibly pulled from oneconformation to another, as illustrated in Figure 3-278.
The elastic fibers thatresult enable skin and other tissues, such as arteries and lungs, to stretch andrecoil without tearing.Intrinsically unstructured regions of proteins are quite frequent in nature,having important functions in the interior of cells.As we have already seen,proteins use the short loops of polypeptide chain that generally protrude from thecore region of protein domains to bind other molecules.
Similarly, many proteins have much longer regions of unstructured amino acid sequences thatinteract with another molecule (often DNA or a protein), undergoing a structural transition to a specific folded conformation when the other molecule isbound. Other proteins appear to resemble elastin, in so far as their functionrequires that they remain largely unstructured. For example, the abundantnucleoporins that coat the inner surface of the nuclear pore complex form a random coil meshwork that is intimately involved in nuclear transport (see Figure12-10). Finally, as will be discussed later in this chapter (see Figure 3-B0C),unstructured regions of polypeptide chain are often used to connect the bindingsites for proteins that function together to catalyze a biological reaction.
Thus,for example, in facilitating cell signaling, large scaffold proteinsuse such flexibleregions as "tethers" that concentrate sets of interacting proteins, often confiningthem to particular sites in the cell (discussedin Chapter 1S).We can recognize the unstructured regions in many proteins by their biasedamino acid composition: they contain very few of the bulky hydrophobic aminoacids that normally form the core of a folded protein, being composed insteadof a high proportion of the amino acids Gln, Ser,Pro, GIu, and Lys.
Such "nativelyunfolded" regions also frequently contain repeated sequencesof amino acids.lular ProteinsCovalent Cross-LinkagesOften StabiIize ExtracelMany protein molecules are either attached to the outside of a cell's plasmamembrane or secreted as part of the extracellular matrix. All such proteins aredirectly exposed to extracellular conditions. To help maintain their structures,the polypeptide chains in such proteins are often stabilized by covalent crossIinkages. These linkages can either tie two amino acids in the same proteintogether, or connect different polypeptide chains in a multisubunit protein.
Themost common cross-linkages in proteins are covalent sulfur-sulfur bonds.These disulfide bonds (also called S-S bonds) form as cells prepare newly synthesized proteins for export. As described in Chapter 12, their formation is catalyzed in the endoplasmic reticulum by an enzyme that links together two pairsof -SH groups of cysteine side chains that are adjacent in the folded protein (Figure 3-28). Disulfide bonds do not change the conformation of a protein butinstead act as atomic stanles to reinforce its most favored conformation. ForSHIoxidants+reductantsauY' '2Figure3-28 Disulfidebonds.
<ATAC>how covalentThisdiagramillustratesinterchain disulfidebondsform betweenadjacentdisulfidethesecysteinesidechains.As indicated,oonocanjoin eithertwo partsofcross-linkageschainor twothe samepolyPePtidedifferentpolypeptidechains.Sincetheenergyrequiredto breakone covalentbond is much largerthan the energyrequiredto breakeven a whole set of2-1, p.53),bonds(seeTablenoncovalenta disulfidebond can havea majorstabilizingeffecton a Protein.148Chapter3: Proteinsh e x a g o n al lypacKeosheeth e l i c Iatubeexample, Iysozyme-an enzyme in tears that dissolves bacterial cell wallsretains its antibacterial activity for a long time because it is stabilized by suchcross-linkages.Disulfide bonds generally fail to form in the cell cytosol, where a high concentration of reducing agents converts S-S bonds back to cysteine -SH groups.Apparently, proteins do not require this tlpe of reinforcement in the relativelymild environment inside the cell.ProteinMoleculesOftenServeasSubunitsfor the AssemblyofLargeStructuresThe same principles that enable a protein molecule to associatewith itself toform rings or filaments also operate to generate much larger structures in thecell-supramolecular structures such as enzyme complexes, ribosomes, proteinfilaments, viruses, and membranes.
These large objects are not made as single,giant, covalently linked molecules. Instead they are formed by the noncovalentassembly of many separatelymanufactured molecules, which serve as the subunits of the final structure.The use of smaller subunits to build larger structures has severaladvantages:l. A large structure built from one or a few repeating smaller subunitsrequires only a small amount of genetic information.2. Both assembly and disassembly can be readily controlled, reversible processes,becausethe subunits associatethrough multiple bonds of relativelylow energy.3.
Errors in the slnthesis of the structure can be more easily avoided, sincecorrection mechanisms can operate during the course of assembly toexclude malformed subunits.Some protein subunits assemble into flat sheets in which the subunits arearranged in hexagonal patterns. Specializedmembrane proteins are sometimesarranged this way in lipid bilayers. with a slight change in rhe geometry of theindividual subunits, a hexagonal sheet can be converted into a tube (Figure3-29) or, with more changes, into a hollow sphere. protein tubes and spheresthat bind specific RNA and DNA molecules in their interior form the coats ofviruses.The formation of closed structures, such as rings, tubes, or spheres,providesadditional stability because it increasesthe number of bonds between the protein subunits.
Moreover, because such a structure is created by mutually dependent, cooperative interactions between subunits, a relatively small change thataffects each subunit individually can cause the structure to assemble or disassemble. These principles are dramatically illustrated in the protein coat or capsld of many simple viruses,which takes the form of a hollow sphere based on anicosahedron (Figure 3-30). capsids are often made of hundreds of identical protein subunits that enclose and protect the viral nucleic acid (Figure 3-31). Theprotein in such a capsid must have a particularly adaptable structure: not onlymust it make severaldifferent kinds of contacts to create the sphere,it must alsochange this arrangement to let the nucleic acid out to initiate viral replicationonce the virus has entered a cell.Figure3-29 An exampleof theassemblyof a singleproteinsubunitrequiringmultiple protein-proteinpackedglobularcontacts.Hexagonallyproteinsubunitscanform eithera flatsheetor a tube.149THESHAPEAND STRUCTUREOF PROTEINS20 nmFigure3-30 The capsidsof someviruses,all shownat the samescale.(A)Tomatobushystuntvirus;(B)poliovirus;(C)simianvirus40 (5Va0);of all of thesecapsidshavebeendetermined(D)satellitetobacconecrosisvirus.Thestructuresand JamesM.
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