2 Структура и функция белка (1160071), страница 25
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The a and /3 subunits are colored as in Fig. 7-26.Part II Structure and Catalysis190There Are Limits to the Size of ProteinsLightchainsTwo supercoileda helicesHeadsThe relatively large size of proteins reflects their functions. The function of an enzyme, for example, requires a protein large enough to forma specifically structured pocket to bind its substrate. The size of proteins has limits, however, imposed by the genetic coding capacity ofnucleic acids and the accuracy of the protein biosynthetic process.
Theuse of many copies of one or a few proteins to make a large enclosingstructure is important for viruses because this strategy conserves genetic material. Remember that there is a linear correspondence between the sequence of a gene in nucleic acid and the amino acid sequence of the protein for which it codes (see Fig.
6-14). The nucleicacids of viruses are much too small to encode the information requiredfor a protein shell made of a single polypeptide. By using many copiesof much smaller proteins for the virus coat, a much shorter nucleic acidis needed for the protein subunits, and this nucleic acid can be efficiently used over and over again. Cells also use large protein complexesin muscle, cilia, the cytoskeleton, and other structures. It is simplymore efficient to make many copies of a small protein than one copy ofa very large one. The second factor limiting the size of proteins is theerror frequency during protein biosynthesis.
This error frequency islow but can become significant for very large proteins. Simply put, thepotential for incorporating a "wrong" amino acid in a protein is greaterfor a large protein than a small one.Some Proteins Form Supramolecular ComplexesThe same principles that govern the stability of secondary, tertiary,and quaternary structure in proteins guide the formation of very largeprotein complexes.
These function, for example, as biological engines^arboxyl/150 nm2 •" /(muscle and cilia), large structural enclosures (virus coats), cellularnmterminus /Tailskeletons (actin and tubulin filaments), DNA-packaging complexes(chromatin), and machines for protein synthesis (ribosomes). In manycases the complex consists of a small number of distinct proteins, spe(a)cialized so that they spontaneously polymerize to form large structures.Muscle provides an example of a supramolecular complex of multiple copies of a limited number of proteins. The contractile force of muscle is generated by the interaction of two proteins, actin and myosin(Chapter 2).
Myosin is a long, rodlike molecule (Mr 540,000) consistingG-actinof six polypeptide chains, two so-called heavy chains (Mr —230,000)subunitsand four light chains (Mr -20,000) (Fig. 7-30a). The two heavy chainshave long a-helical tails that twist around each other in a left-handed20nmfashion. The large head domain, at one end of each heavy chain, interacts with actin and contains a catalytic site for ATP hydrolysis. Manymyosin molecules assemble together to form the thick filaments ofskeletal muscle (Fig. 7-31).36 nmThe other protein, actin, is a polymer of the globular protein(b)G-actin (Mr 42,000); two such polymers coil around each other in aright-handed helix to form a thin filament (Fig. 7-30b).
The interacFigure 7-30 Myosin and actin, the two filamention between actin and myosin is dynamic; contacts consist of multipletous proteins of contractile systems, (a) The myosinmolecule has a long tail consisting of two superweak interactions that are strong enough to provide a stable associacoiled a-helical polypeptide chains (heavy chains).tion but weak enough to allow dissociation when needed. Hydrolysis ofThe head of each heavy chain is associated withATP in the myosin head is coupled to a series of conformationaltwo light chains and is an enzyme capable of hychanges that bring about muscle contraction (Fig.
7-32). A similardrolyzing ATP. (b) A representation of an F-actinfiber, which consists of two chains of G-actin subengine involving an interaction between tubulin and dynein bringsunits coiled about each other to form a filament.about the motion of cilia (Chapter 2).20nmVChapter 7 The Three-Dimensional Structure of ProteinsFigure 7—31 The thick and thin filaments of muscle. Many myosin molecules assemble in a bundleto form a thick filament.
Muscle contraction involves the sliding of thick filaments past thin filaments of actin, by a mechanism described in Fig.7-32.ActinfilamentATP hydrolyzed to ADPand Pj, which remainassociated with myosinheadMyosin head attaches toactin filamentPi and ADP released;myosin head undergoesconformational changePj.moves the actin and*4 that moveJADP I myosini filamentsrelativefil;notherI to one anoATP binds to myosin head,causing dissociationfrom actinFigure 7-32 The sliding of the thick and thin filaments in muscle involves an interaction betweenactin and myosin mediated by ATP hydrolysis(ATP ^ ADP + Pj, where Pj is inorganic phosphate,or PO4").
Conformational changes in the myosinhead that are coupled to stages in the ATP hydrolytic cycle cause myosin to successively dissociatefrom one actin subunit and then associate withanother farther along the actin filament. In thisway the myosin heads "walk" along the thin filaments, and draw the thin filament array into thethick filament array.191192Part II Structure and CatalysisThe protein structures in virus coats (called capsids) generallyfunction simply as enclosures. In many cases capsids are made up ofone or a few proteins that assemble spontaneously around a viral DNAor RNA molecule. Two types of viral structures are shown in Figure7-33. The tobacco mosaic virus is a right-handed helical filament with2,130 copies of a single protein that interact to form a cylinder enclosing the RNA genome. Another common structure for virus coats is theicosahedron, a regular 12-cornered polyhedron having 20 equilateraltriangular faces.
Two examples are poliovirus and human rhinovirus14 (a common cold virus), each made up of 60 protein units (Fig. 7-33).Each protein unit consists of single copies of four different polypeptidechains, three of which are accessible at the outer surface. The resultingshell encloses the genetic material (RNA) of the virus.The primary forces guiding the assembly of even these very largestructures are the weak noncovalent interactions that have dominatedthis discussion. Each protein has several surfaces that are complementary to surfaces in adjacent protein subunits. Each protein is moststable only when it is part of the larger structure.RNAProteinsubunitFigure 7-33 Supramolecular complexes. The coatstructures of (a) tobacco mosaic virus, (b) rhinovirus 14 (a human cold virus), and (c) poliovirus.
Inthe latter two, the proteins assemble into a stablestructure called an icosahedron (illustrated abovethe photos). The rod-shaped tobacco mosaic virus is300 nm long and 18 nm in diameter. Bothrhinovirus 14 and poliovirus have diameters ofabout 30 nm.(b)(c)Chapter 7 The Three-Dimensional Structure of ProteinsEvery protein has a unique three-dimensionalstructure that reflects its function, a structure stabilized by multiple weak interactions.
Hydrophobicinteractions provide the major contribution to stabilizing the globular form of most soluble proteins;hydrogen bonds and ionic interactions are optimized in the specific structure that is thermodynamically most stable.There are four generally recognized levels ofprotein structure. Primary structure refers to theamino acid sequence and the location of disulfidebonds. Secondary structure refers to the spatialrelationship of adjacent amino acids. Tertiarystructure is the three-dimensional conformation ofan entire polypeptide chain.
Quaternary structureinvolves the spatial relationship of multiple polypeptide chains (e.g., enzyme subunits) that aretightly associated.The nature of the bonds in the polypeptidechain places constraints on structure. The peptidebond is characterized by a partial double-bondcharacter that keeps the entire amide group in arigid planar configuration. The N—Ca and Crt—Cbonds can rotate with bond angles cf> and <//, respectively. Secondary structure can be defined completely by these two bond angles.There are two general classes of proteins: fibrous and globular. Fibrous proteins, which servemainly structural roles, have simple repeatingstructures and provided excellent models for theearly studies of protein structure. Two major typesof secondary structure were predicted by modelbuilding based on information obtained from fibrous proteins: the a helix and the /3 conformation.Both are characterized by optimal hydrogen bonding between amide nitrogens and carbonyl oxygensin the peptide backbone.
The stability of thesestructures within a protein is influenced by theiramino acid content and by the relative placementof amino acids in the sequence. Another nonrepeating type of secondary structure common in proteinsis the /3 bend.In fibrous proteins such as keratin and collagen,a single type of secondary structure predominates.The polypeptide chains are supertwisted into ropesand then combined in larger bundles to providestrength.
The structure of elastin permits stretching.Globular proteins have more complicated tertiary structures, often containing several typesof secondary structure in the same polypeptidechain. The first globular protein structure to be193determined, using x-ray diffraction methods, wasthat of myoglobin. This structure confirmed that apredicted secondary structure (a helix) occurs inproteins; that hydrophobic amino acids are locatedin the protein interior; and that globular proteinsare compact. Subsequent research on proteinstructure has reinforced these conclusions whiledemonstrating that different proteins often differin tertiary structure.The three-dimensional structure of proteins canbe destroyed by treatments that disrupt weak interactions, a process called denaturation.
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