B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 44
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When the denaturingsolvent is removed, the protein often refolds spontaneously, or renatures, into itsoriginal conformation. This indicates that the amino acid sequence contains all ofthe information needed for specifying the three-dimensional shape of a protein, acritical point for understanding cell biology.Most proteins fold up into a single stable conformation. However, this conformation changes slightly when the protein interacts with other molecules in thecell. This change in shape is often crucial to the function of the protein, as we seelater.Although a protein chain can fold into its correct conformation without outside help, in a living cell special proteins called molecular chaperones often assistin protein folding.
Molecular chaperones bind to partly folded polypeptide chainsand help them progress along the most energetically favorable folding pathway. Inthe crowded conditions of the cytoplasm, chaperones are required to prevent thetemporarily exposed hydrophobic regions in newly synthesized protein chainsfrom associating with each other to form protein aggregates (see p. 355). However,the final three-dimensional shape of the protein is still specified by its amino acidsequence: chaperones simply make reaching the folded state more reliable.Figure 3–5 How a protein folds into acompact conformation.
The polar aminoacid side chains tend to lie on the outsideof the protein, where they can interact withwater; the nonpolar amino acid side chainsare buried on the inside forming a tightlypacked hydrophobic core of atoms thatare hidden from water. In this schematicdrawing, the protein contains only about35 amino acids.THE SHAPE AND STRUCTURE OF PROTEINS115Figure 3–6 Four representationsdescribing the structure of a smallprotein domain.
Constructed from a stringof 100 amino acids, the SH2 domain is partof many different proteins (see, for example,Figure 3–61). Here, the structure of theSH2 domain is displayed as (A) apolypeptide backbone model, (B) a ribbonmodel, (C) a wire model that includes theamino acid side chains, and (D) a spacefilling model (Movie 3.1).
These imagesare colored in a way that allows thepolypeptide chain to be followed from itsN-terminus (purple) to its C-terminus (red)(PDB code: 1SHA).Proteins come in a wide variety of shapes, and most are between 50 and2000 amino acids long. Large proteins usually consist of several distinct proteindomains—structural units that fold more or less independently of each other, aswe discuss below. The structure of even a small domain is complex, and for clarity,several different representations are conventionally used, each of which emphasizes distinct features. As an example, Figure 3–6 presents four representationsof a protein domain calledSH2,a structure present in many different proteins inMBoC6n3.101/3.06eukaryotic cells and involved in cell signaling (see Figure 15–46).Descriptions of protein structures are aided by the fact that proteins are builtup from combinations of several common structural motifs, as we discuss next.The α Helix and the β Sheet Are Common Folding PatternsWhen we compare the three-dimensional structures of many different proteinmolecules, it becomes clear that, although the overall conformation of each protein is unique, two regular folding patterns are often found within them.
Both patterns were discovered more than 60 years ago from studies of hair and silk. Thefirst folding pattern to be discovered, called the α helix, was found in the proteinα-keratin, which is abundant in skin and its derivatives—such as hair, nails, andhorns. Within a year of the discovery of the α helix, a second folded structure,called a β sheet, was found in the protein fibroin, the major constituent of silk.These two patterns are particularly common because they result from hydrogen-bonding between the N–H and C=O groups in the polypeptide backbone,without involving the side chains of the amino acids. Thus, although incompatiblewith some amino acid side chains, many different amino acid sequences can formthem. In each case, the protein chain adopts a regular, repeating conformation.Figure 3–7 illustrates the detailed structures of these two important conformations, which in ribbon models of proteins are represented by a helical ribbon andby a set of aligned arrows, respectively.Chapter 3: Proteins116amino acidside chainH-bondhydrogenamino acidside chainRRcarbonRRoxygenRpeptidebondhydrogenRRnitrogenRR(B)RRRRRRoxygencarbonnitrogen0.7 nmcarbonRRRRR0.54 nmH-bondcarbon(A)RnitrogenRR(C)R(D)Figure 3–7 The regular conformation of the polypeptide backbone in the α helix and the β sheet.
The α helix is shown in(A) and (B). The N–H of every peptide bond is hydrogen-bonded to the C=O of a neighboring peptide bond located four peptidebonds away in the same chain. Note that all of the N–H groups point up in this diagram and that all of the C=O groups pointdown (toward the C-terminus); this gives a polarity to the helix, with the C-terminus having a partial negative and the N-terminusa partial positive charge (Movie 3.2). The β sheet is shown in (C) and (D). In this example, adjacent peptide chains run inopposite (antiparallel) directions.
Hydrogen-bonding between peptide bonds in different strands holds the individual polypeptidechains (strands) together in a β sheet, and the amino acid side chains in each strand alternately project above and below theplane of the sheet (Movie 3.3). (A) and (C) show all the atoms in the polypeptide backbone, but the amino acid side chains aretruncated and denoted by R. In contrast, (B) and (D) show only the carbon and nitrogen backbone atoms.MBoC6 m3.07/3.07The cores of many proteins contain extensive regions of β sheet. As shownin Figure 3–8, these β sheets can form either from neighboring segments of thepolypeptide backbone that run in the same orientation (parallel chains) or froma polypeptide backbone that folds back and forth upon itself, with each sectionof the chain running in the direction opposite to that of its immediate neighbors (antiparallel chains).
Both types of β sheet produce a very rigid structure,held together by hydrogen bonds that connect the peptide bonds in neighboringchains (see Figure 3–7C).An α helix is generated when a single polypeptide chain twists around on itselfto form a rigid cylinder. A hydrogen bond forms between every fourth peptidebond, linking the C=O of one peptide bond to the N–H of another (see Figure3–7A). This gives rise to a regular helix with a complete turn every 3.6 amino acids.The SH2 protein domain illustrated in Figure 3–6 contains two α helices, as well asa three-stranded antiparallel β sheet.Regions of α helix are abundant in proteins located in cell membranes, suchas transport proteins and receptors.
As we discuss in Chapter 10, those portionsof a transmembrane protein that cross the lipid bilayer usually cross as α helices composed largely of amino acids with nonpolar side chains. The polypeptidebackbone, which is hydrophilic, is hydrogen-bonded to itself in the α helix andshielded from the hydrophobic lipid environment of the membrane by its protruding nonpolar side chains (see also Figure 3–75A).In other proteins, α helices wrap around each other to form a particularly stable structure, known as a coiled-coil. This structure can form when the two (or insome cases, three or four) α helices have most of their nonpolar (hydrophobic)side chains on one side, so that they can twist around each other with these sidechains facing inward (Figure 3–9).
Long rodlike coiled-coils provide the structuralTHE SHAPE AND STRUCTURE OF PROTEINS117framework for many elongated proteins. Examples are α-keratin, which forms theintracellular fibers that reinforce the outer layer of the skin and its appendages,and the myosin molecules responsible for muscle contraction.(A)Protein Domains Are Modular Units from Which Larger ProteinsAre BuiltEven a small protein molecule is built from thousands of atoms linked together byprecisely oriented covalent and noncovalent bonds. Biologists are aided in visualizing these extremely complicated structures by various graphic and computer-based three-dimensional displays.
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