B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 45
Текст из файла (страница 45)
The student resource site that accompaniesthis book contains computer-generated images of selected proteins, displayedand rotated on the screen in a variety of formats.Scientists distinguish four levels of organization in the structure of a protein.The amino acid sequence is known as the primary structure. Stretches of polypeptide chain that form α helices and β sheets constitute the protein’s secondary structure.
The full three-dimensional organization of a polypeptide chain issometimes referred to as the tertiary structure, and if a particular protein molecule is formed as a complex of more than one polypeptide chain, the completestructure is designated as the quaternary structure.Studies of the conformation, function, and evolution of proteins have alsorevealed the central importance of a unit of organization distinct from these four.This is the protein domain, a substructure produced by any contiguous part ofa polypeptide chain that can fold independently of the rest of the protein into acompact, stable structure.
A domain usually contains between 40 and 350 aminoacids, and it is the modular unit from which many larger proteins are constructed.The different domains of a protein are often associated with different functions. Figure 3–10 shows an example—the Src protein kinase, which functions insignaling pathways inside vertebrate cells (Src is pronounced “sarc”). This protein(B)Figure 3–8 Two types of β sheetstructures.
(A) An antiparallel β sheet (seeFigure 3–7C). (B) A parallel β sheet. Both ofthese structures are common in proteins.MBoC6 m3.08/3.08NH 2aedaNH2edNH2agstripe ofhydrophobic“a” and “d”amino acidsdag11 nmdcgadchelices wrap around each other to minimizeexposure of hydrophobic amino acidside chains to aqueous environmentgHOOC COOH0.5 nm(A)(B)(C)Figure 3–9 A coiled-coil. (A) A single αhelix, with successive amino acid sidechains labeled in a sevenfold sequence,“abcdefg” (from bottom to top). Aminoacids “a” and “d” in such a sequence lieclose together on the cylinder surface,forming a “stripe” (green) that windsslowly around the α helix. Proteins thatform coiled-coils typically have nonpolaramino acids at positions “a” and “d.”Consequently, as shown in (B), the two αhelices can wrap around each other withthe nonpolar side chains of one α helixinteracting with the nonpolar side chainsof the other.
(C) The atomic structureof a coiled-coil determined by x-raycrystallography. The alpha helical backboneis shown in red and the nonpolar sidechains in green, while the more hydrophilicamino acid side chains, shown in gray, areleft exposed to the aqueous environment(Movie 3.4). (PDB code: 3NMD.)Chapter 3: Proteins118Figure 3–10 A protein formed frommultiple domains. In the Src proteinshown, a C-terminal domain with two lobes(yellow and orange) forms a protein kinaseenzyme, while the SH2 and SH3 domainsperform regulatory functions. (A) A ribbonmodel, with ATP substrate in red. (B) Aspace-filling model, with ATP substrate inred. Note that the site that binds ATP ispositioned at the interface of the two lobesthat form the kinase.
The structure of theSH2 domain was illustrated in Figure 3–6.(PDB code: 2SRC.)SH3 domainATP(A)SH2 domain(B)is considered to have three domains: the SH2 and SH3 domains have regulatoryroles, while the C-terminal domain is responsible for the kinase catalytic activity.Later in the chapter, we shall return to this protein, in order to explain how proteins can form molecular switches that transmit information throughout cells.Figure 3–11 presents ribbon models of three differently organized proteindomains. As these examples illustrate, the central core of a domain can be constructed from α helices, from β sheets, or from various combinations of these twofundamental folding elements.MBoC6m3.10/3.10The smallest protein moleculescontainonly a single domain, whereas largerproteins can contain several dozen domains, often connected to each other byshort, relatively unstructured lengths of polypeptide chain that can act as flexiblehinges between domains.Few of the Many Possible Polypeptide Chains Will Be Usefulto CellsSince each of the 20 amino acids is chemically distinct and each can, in principle, occur at any position in a protein chain, there are 20 × 20 × 20 × 20 = 160,000different possible polypeptide chains four amino acids long, or 20n different possible polypeptide chains n amino acids long.
For a typical protein length of about300 amino acids, a cell could theoretically make more than 10390 (20300) differentpolypeptide chains. This is such an enormous number that to produce just onemolecule of each kind would require many more atoms than exist in the universe.Only a very small fraction of this vast set of conceivable polypeptide chainswould adopt a stable three-dimensional conformation—by some estimates, less(A)(B)(C)Figure 3–11 Ribbon models of threedifferent protein domains.
(A) Cytochromeb562, a single-domain protein involved inelectron transport in mitochondria. Thisprotein is composed almost entirely ofα helices. (B) The NAD-binding domain ofthe enzyme lactic dehydrogenase, whichis composed of a mixture of α helices andparallel β sheets. (C) The variable domainof an immunoglobulin (antibody) lightchain, composed of a sandwich of twoantiparallel β sheets. In these examples, theα helices are shown in green, while strandsorganized as β sheets are denoted by redarrows. Note how the polypeptide chaingenerally traverses back and forth acrossthe entire domain, making sharp turns onlyat the protein surface (Movie 3.5). It is theprotruding loop regions (yellow) that oftenform the binding sites for other molecules.(Adapted from drawings courtesy of JaneRichardson.)THE SHAPE AND STRUCTURE OF PROTEINS119than one in a billion. And yet the majority of proteins present in cells do adoptunique and stable conformations.
How is this possible? The answer lies in natural selection. A protein with an unpredictably variable structure and biochemicalactivity is unlikely to help the survival of a cell that contains it. Such proteins wouldtherefore have been eliminated by natural selection through the enormously longtrial-and-error process that underlies biological evolution.Because evolution has selected for protein function in living organisms, theamino acid sequence of most present-day proteins is such that a single conformation is stable.
In addition, this conformation has its chemical properties finelytuned to enable the protein to perform a particular catalytic or structural functionin the cell. Proteins are so precisely built that the change of even a few atoms inone amino acid can sometimes disrupt the structure of the whole molecule soseverely that all function is lost.
And, as discussed later in this chapter, when certain rare protein misfolding accidents occur, the results can be disastrous for theorganisms that contain them.Proteins Can Be Classified into Many FamiliesOnce a protein had evolved that folded up into a stable conformation with useful properties, its structure could be modified during evolution to enable it toperform new functions. This process has been greatly accelerated by geneticmechanisms that occasionally duplicate genes, allowing one gene copy to evolveindependently to perform a new function (discussed in Chapter 4). This type ofevent has occurred very often in the past; as a result, many present-day proteinscan be grouped into protein families, each family member having an amino acidsequence and a three-dimensional conformation that resemble those of the otherfamily members.Consider, for example, the serine proteases, a large family of protein-cleaving(proteolytic) enzymes that includes the digestive enzymes chymotrypsin, trypsin,and elastase, and several proteases involved in blood clotting.
When the protease portions of any two of these enzymes are compared, parts of their amino acidsequences are found to match. The similarity of their three-dimensional conformations is even more striking: most of the detailed twists and turns in theirpolypeptide chains, which are several hundred amino acids long, are virtuallyidentical (Figure 3–12). The many different serine proteases nevertheless havedistinct enzymatic activities, each cleaving different proteins or the peptide bondsbetween different types of amino acids. Each therefore performs a distinct function in an organism.The story we have told for the serine proteases could be repeated for hundredsof other protein families.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
