H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 26
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As a consequence ofthe peptide linkage, the backbone exhibits directionality because all the amino groups are located on the same side ofthe C atoms. Thus one end of a protein has a free (unlinked)amino group (the N-terminus) and the other end has a freecarboxyl group (the C-terminus). The sequence of a proteinchain is conventionally written with its N-terminal aminoacid on the left and its C-terminal amino acid on the right.3.1 • Hierarchical Structure of Proteinsaa1Raa2aa3PeptidebondRRPeptidebond▲ FIGURE 3-2 Structure of a tripeptide. Peptide bonds(yellow) link the amide nitrogen atom (blue) of one amino acid(aa) with the carbonyl carbon atom (gray) of an adjacent one inthe linear polymers known as peptides or polypeptides,depending on their length.
Proteins are polypeptides that havefolded into a defined three-dimensional structure (conformation).The side chains, or R groups (green), extending from the carbon atoms (black) of the amino acids composing a proteinlargely determine its properties. At physiological pH values, theterminal amino and carboxyl groups are ionized.The primary structure of a protein is simply the lineararrangement, or sequence, of the amino acid residues thatcompose it.
Many terms are used to denote the chainsformed by the polymerization of amino acids. A short chainof amino acids linked by peptide bonds and having a definedsequence is called a peptide; longer chains are referred to aspolypeptides. Peptides generally contain fewer than 20–30amino acid residues, whereas polypeptides contain as manyas 4000 residues. We generally reserve the term protein fora polypeptide (or for a complex of polypeptides) that has awell-defined three-dimensional structure.
It is implied thatproteins and peptides are the natural products of a cell.The size of a protein or a polypeptide is reported as itsmass in daltons (a dalton is 1 atomic mass unit) or as its molecular weight (MW), which is a dimensionless number. Forexample, a 10,000-MW protein has a mass of 10,000 daltons(Da), or 10 kilodaltons (kDa). In the last section of this chapter, we will consider different methods for measuring the sizesand other physical characteristics of proteins. The known andpredicted proteins encoded by the yeast genome have an average molecular weight of 52,728 and contain, on average,466 amino acid residues. The average molecular weight ofamino acids in proteins is 113, taking into account their average relative abundance.
This value can be used to estimate thenumber of residues in a protein from its molecular weight or,conversely, its molecular weight from the number of residues.Secondary Structures Are the Core Elementsof Protein ArchitectureThe second level in the hierarchy of protein structure consistsof the various spatial arrangements resulting from the folding of localized parts of a polypeptide chain; these arrangements are referred to as secondary structures.
A single61polypeptide may exhibit multiple types of secondary structure depending on its sequence. In the absence of stabilizingnoncovalent interactions, a polypeptide assumes a randomcoil structure. However, when stabilizing hydrogen bondsform between certain residues, parts of the backbone foldinto one or more well-defined periodic structures: the alpha() helix, the beta () sheet, or a short U-shaped turn. In anaverage protein, 60 percent of the polypeptide chain exist as helices and sheets; the remainder of the molecule is inrandom coils and turns.
Thus, helices and sheets are themajor internal supportive elements in proteins. In this section, we explore forces that favor the formation of secondarystructures. In later sections, we examine how these structurescan pack into larger arrays.The Helix In a polypeptide segment folded into an helix,the carbonyl oxygen atom of each peptide bond is hydrogenbonded to the amide hydrogen atom of the amino acid fourresidues toward the C-terminus. This periodic arrangement ofbonds confers a directionality on the helix because all thehydrogen-bond donors have the same orientation (Figure 3-3).RRRRR3.6 residues perhelical turnRRRRRRRR▲ FIGURE 3-3 The helix, a common secondary structurein proteins. The polypeptide backbone (red) is folded into a spiralthat is held in place by hydrogen bonds between backboneoxygen and hydrogen atoms.
The outer surface of the helix iscovered by the side-chain R groups (green).62CHAPTER 3 • Protein Structure and Function FIGURE 3-4 The sheet, another commonsecondary structure in proteins. (a) Top view ofa simple two-stranded sheet with antiparallel strands. The stabilizing hydrogen bonds betweenthe strands are indicated by green dashed lines.The short turn between the strands also is stabilizedby a hydrogen bond.
(b) Side view of a sheet.The projection of the R groups (green) above andbelow the plane of the sheet is obvious in this view.The fixed angle of the peptide bond produces apleated contour.(a)RRRRRRRRRRR(b)RRRThe stable arrangement of amino acids in the helix holdsthe backbone in a rodlike cylinder from which the side chainspoint outward. The hydrophobic or hydrophilic quality of thehelix is determined entirely by the side chains because thepolar groups of the peptide backbone are already engaged inhydrogen bonding in the helix.The Sheet Another type of secondary structure, the sheet,consists of laterally packed strands. Each strand is a short(5- to 8-residue), nearly fully extended polypeptide segment.Hydrogen bonding between backbone atoms in adjacent strands, within either the same polypeptide chain or betweendifferent polypeptide chains, forms a sheet (Figure 3-4a).
Theplanarity of the peptide bond forces a sheet to be pleated;hence this structure is also called a pleated sheet, or simply apleated sheet. Like helices, strands have a directionality defined by the orientation of the peptide bond. Therefore, in apleated sheet, adjacent strands can be oriented in the same(parallel) or opposite (antiparallel) directions with respect toeach other.
In both arrangements, the side chains project fromboth faces of the sheet (Figure 3-4b). In some proteins, sheetsform the floor of a binding pocket; the hydrophobic core ofother proteins contains multiple sheets.Turns Composed of three or four residues, turns are locatedon the surface of a protein, forming sharp bends that redirectthe polypeptide backbone back toward the interior. Theseshort, U-shaped secondary structures are stabilized by a hydrogen bond between their end residues (see Figure 3-4a).Glycine and proline are commonly present in turns. The lackof a large side chain in glycine and the presence of a built-inbend in proline allow the polypeptide backbone to fold intoa tight U shape. Turns allow large proteins to fold into highlycompact structures. A polypeptide backbone also may contain longer bends, or loops.
In contrast with turns, which ex-RRRRRRRRRRRR Rhibit just a few well-defined structures, loops can be formedin many different ways.Overall Folding of a Polypeptide Chain YieldsIts Tertiary StructureTertiary structure refers to the overall conformation of apolypeptide chain—that is, the three-dimensional arrangement of all its amino acid residues.
In contrast with secondary structures, which are stabilized by hydrogen bonds,tertiary structure is primarily stabilized by hydrophobic interactions between the nonpolar side chains, hydrogen bondsbetween polar side chains, and peptide bonds. These stabilizing forces hold elements of secondary structure— helices, strands, turns, and random coils—compactly together.Because the stabilizing interactions are weak, however, thetertiary structure of a protein is not rigidly fixed but undergoes continual and minute fluctuation.
This variation instructure has important consequences in the function andregulation of proteins.Different ways of depicting the conformation of proteinsconvey different types of information. The simplest way torepresent three-dimensional structure is to trace the course ofthe backbone atoms with a solid line (Figure 3-5a); the mostcomplex model shows every atom (Figure 3-5b). The former,a C trace, shows the overall organization of the polypeptidechain without consideration of the amino acid side chains;the latter, a ball-and-stick model, details the interactions between side-chain atoms, which stabilize the protein’s conformation, as well as the atoms of the backbone.
Even thoughboth views are useful, the elements of secondary structure arenot easily discerned in them. Another type of representationuses common shorthand symbols for depicting secondarystructure—for example, coiled ribbons or solid cylinders for helices, flat ribbons or arrows for strands, and flexible3.1 • Hierarchical Structure of Proteins(a) Cα backbone trace(c) Ribbons FIGURE 3-5 Various graphic(b) Ball and stick(d) Solvent-accessible surfacethin strands for turns and loops (Figure 3-5c).
This type ofrepresentation makes the secondary structures of a proteineasy to see.However, none of these three ways of representing protein structure convey much information about the proteinsurface, which is of interest because it is where other molecules bind to a protein. Computer analysis can identify thesurface atoms that are in contact with the watery environment. On this water-accessible surface, regions having acommon chemical character (hydrophobicity or hydrophilicity) and electrical character (basic or acidic) can be mapped.Such models reveal the topography of the protein surface andthe distribution of charge, both important features of binding sites, as well as clefts in the surface where small molecules often bind (Figure 3-5d).
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