B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 49
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For example, it is this tethering function that allows substrates to movebetween active sites in large multienzyme complexes (see Figure 3–54). A similar tethering function allows large scaffold proteins with multiple protein-bindingsites to concentrate sets of interacting proteins, both increasing reaction rates andconfining their reaction to a particular site in a cell (see Figure 3–78).Like elastin, other proteins have a function that directly requires that theyremain largely unstructured. Thus, large numbers of disordered protein chainsin close proximity can create micro-regions of gel-like consistency inside the cellthat restrict diffusion. For example, the abundant nucleoporins that coat the innersurface of the nuclear pore complex form a random coil meshwork (Figure 3–24)that is critical for selective nuclear transport (see Figure 12–8).P+PPPPP(A)BINDING(B)SIGNALING(C)TETHERING(D)DIFFUSION BARRIERFigure 3–24 Some important functionsfor intrinsically disordered proteinsequences.
(A) Unstructured regionsof polypeptide chain often form bindingsites for other proteins. Although thesebinding events are of high specificity,they are often of low affinity due to thefree-energy cost of folding the normallyunfolded partner (and they are thus readilyreversible). (B) Unstructured regions canbe easily modified covalently to changetheir binding preferences, and they aretherefore frequently involved in cell signalingprocesses. In this schematic, multiple sitesof protein phosphorylation are indicated.(C) Unstructured regions frequently create“tethers” that hold interacting proteindomains in close proximity. (D) A densenetwork of unstructured proteins can forma diffusion barrier, as the nucleoporins dofor the nuclear pore.THE SHAPE AND STRUCTURE OF PROTEINS127cysteineCCCH2CH2SHSSHCCH2SHSHCH2CSCH2COXIDATIONREDUCTIONCH2CCinterchaindisulfidebondCH2SSintrachaindisulfidebondCH2CCovalent Cross-Linkages Stabilize Extracellular ProteinsMany protein molecules are either attached to the outside of a cell’s plasma memMBoC6 e4.26/3.24brane or secreted as part of theextracellular matrix.
All such proteins are directlyexposed to extracellular conditions. To help maintain their structures, the polypeptide chains in such proteins are often stabilized by covalent cross-linkages.These linkages can either tie together two amino acids in the same protein, orconnect different polypeptide chains in a multisubunit protein.
Although manyother types exist, the most common cross-linkages in proteins are covalent sulfur–sulfur bonds. These disulfide bonds (also called S–S bonds) form as cells preparenewly synthesized proteins for export. As described in Chapter 12, their formationis catalyzed in the endoplasmic reticulum by an enzyme that links together twopairs of –SH groups of cysteine side chains that are adjacent in the folded protein(Figure 3–25). Disulfide bonds do not change the conformation of a protein butinstead act as atomic staples to reinforce its most favored conformation.
For example, lysozyme—an enzyme in tears that dissolves bacterial cell walls—retains itsantibacterial activity for a long time because it is stabilized by such cross-linkages.Disulfide bonds generally fail to form in the cytosol, where a high concentration of reducing agents converts S–S bonds back to cysteine –SH groups. Apparently, proteins do not require this type of reinforcement in the relatively mild environment inside the cell.Protein Molecules Often Serve as Subunits for the Assembly ofLarge StructuresThe same principles that enable a protein molecule to associate with itself to formrings or a long filament also operate to generate much larger structures formedfrom a set of different macromolecules, such as enzyme complexes, ribosomes,viruses, and membranes. These large objects are not made as single, giant, covalently linked molecules.
Instead they are formed by the noncovalent assembly ofmany separately manufactured molecules, which serve as the subunits of the finalstructure.The use of smaller subunits to build larger structures has several advantages:1. A large structure built from one or a few repeating smaller subunits requiresonly a small amount of genetic information.2. Both assembly and disassembly can be readily controlled reversible processes, because the subunits associate through multiple bonds of relativelylow energy.3.
Errors in the synthesis of the structure can be more easily avoided, sincecorrection mechanisms can operate during the course of assembly toexclude malformed subunits.Figure 3–25 Disulfide bonds. Covalentdisulfide bonds form between adjacentcysteine side chains. These crosslinkages can join either two parts of thesame polypeptide chain or two differentpolypeptide chains. Since the energyrequired to break one covalent bond ismuch larger than the energy required tobreak even a whole set of noncovalentbonds (see Table 2–1, p.
45), a disulfidebond can have a major stabilizing effect ona protein (Movie 3.7).128Chapter 3: ProteinshexagonallypackedsheetsubunittubeFigure 3–26 Single protein subunits formprotein assemblies that feature multipleprotein–protein contacts. Hexagonallypacked globular protein subunits areshown here forming either flat sheets ortubes. Generally, such large structures arenot considered to be single “molecules.”Instead, like the actin filament describedpreviously, they are viewed as assembliesformed of many different molecules.Some protein subunits assemble into flat sheets in which the subunits arearranged in hexagonal patterns.
Specialized membrane proteins are sometimesarranged this way in lipid bilayers. With a slight change in the geometry of theindividual subunits, a hexagonal sheet can be converted into a tube (Figure 3–26)or, with more changes, into a hollow sphere. Protein tubes and spheres that bindspecific RNA and DNA molecules in their interior form the coats of viruses.The formation of closed structures, such as rings, tubes, or spheres, providesadditional stability because it increases the number of bonds between the proteinMBoC6 m3.29/3.25subunits.
Moreover, because such a structureis created by mutually dependent,cooperative interactions between subunits, a relatively small change that affectseach subunit individually can cause the structure to assemble or disassemble.These principles are dramatically illustrated in the protein coat or capsid of manysimple viruses, which takes the form of a hollow sphere based on an icosahedron(Figure 3–27).
Capsids are often made of hundreds of identical protein subunitsthat enclose and protect the viral nucleic acid (Figure 3–28). The protein in sucha capsid must have a particularly adaptable structure: not only must it makeseveral different kinds of contacts to create the sphere, it must also change thisarrangement to let the nucleic acid out to initiate viral replication once the virushas entered a cell.Many Structures in Cells Are Capable of Self-AssemblyThe information for forming many of the complex assemblies of macromoleculesin cells must be contained in the subunits themselves, because purified subunitscan spontaneously assemble into the final structure under the appropriate conditions.
The first large macromolecular aggregate shown to be capable of self-assembly from its component parts was tobacco mosaic virus (TMV ). This virus isa long rod in which a cylinder of protein is arranged around a helical RNA core(Figure 3–29). If the dissociated RNA and protein subunits are mixed together insolution, they recombine to form fully active viral particles. The assembly processis unexpectedly complex and includes the formation of double rings of protein,which serve as intermediates that add to the growing viral coat.Another complex macromolecular aggregate that can reassemble from itscomponent parts is the bacterial ribosome.
This structure is composed of about55 different protein molecules and 3 different rRNA molecules. Incubating a mixture of the individual components under appropriate conditions in a test tubecauses them to spontaneously re-form the original structure. Most importantly,such reconstituted ribosomes are able to catalyze protein synthesis. As might beexpected, the reassembly of ribosomes follows a specific pathway: after certainproteins have bound to the RNA, this complex is then recognized by other proteins, and so on, until the structure is complete.It is still not clear how some of the more elaborate self-assembly processesare regulated.
Many structures in the cell, for example, seem to have a preciselydefined length that is many times greater than that of their component macromolecules. How such length determination is achieved is in many cases a mystery. In20 nmFigure 3–27 The protein capsid of avirus. The structure of the simian virusSV40 capsid has been determined by x-raycrystallographyand, asfor the capsids ofMBoC6m3.30/3.26many other viruses, it is known in atomicdetail. (Courtesy of Robert Grant, StephanCrainic, and James M. Hogle.)THE SHAPE AND STRUCTURE OF PROTEINS129three dimersfree dimersdimerincompleteparticleviral RNAprojecting domainshell domainconnecting armRNA-binding domainfreedimersFigure 3–28 The structure of a sphericalvirus.
In viruses, many copies of a singleprotein subunit often pack togetherto create a spherical shell (a capsid).This capsid encloses the viral genome,composed of either RNA or DNA (see alsoFigure 3–27). For geometric reasons, nomore than 60 identical subunits can packtogether in a precisely symmetric way. Ifslight irregularities are allowed, however,more subunits can be used to producea larger capsid that retains icosahedralsymmetry.
The tomato bushy stunt virus(TBSV) shown here, for example, is aspherical virus about 33 nm in diameterformed from 180 identical copies of a386-amino-acid capsid protein plus anRNA genome of 4500 nucleotides. Toconstruct such a large capsid, the proteinmust be able to fit into three somewhatdifferent environments. This requires threeslightly different conformations, each ofwhich is differently colored in the virusparticle shown here. The postulatedpathway of assembly is shown; the precisethree-dimensional structure has beendetermined by x-ray diffraction. (Courtesyof Steve Harrison.)intact virusparticle(90 dimers)capsid proteinmonomershown asribbonmodel10 nmthe simplest case, a long core protein or other macromolecule provides a scaffoldthat determines the extent of the final assembly.
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