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Relative Orientation of Close-Packed ,8-Pleated Sheets in Proteins

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Relative Orientation of Close-Packed ,8-Pleated Sheets in Proteins Proc. Nati Acad. Sci. USA Vol. 78, No. 7, pp. 4146-4150, July 1981 Biochemistry Relative orientation of close-packed ,8-pleated sheets in proteins (twisted ,3sheets/protein secondary and tertiary structure) CYRUS CHOTHIA*t AND JOEL JANINt *William Ramsay, Ralph Foster and Christopher Ingold Laboratories, University College London, Gower Street, London WC1E 6BT, England; tMedical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, England; and *Unit6 de Biochimie Cellulaire, Department de Biochimie et Gen~tique Moleculaire, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France Communicated by Max F. Perutz, March 30, 1981 ABSTRACT When (3-pleated sheets pack face to face in pro- curve from left to right, while those that point down curve from teins, the angle between the strand directions ofthe two (3-sheets right to left. is observed to be near -30°. We propose a simple model for f3- Fig. 2 b and c illustrates some of the effects of twisting two sheet-to-(-sheet packing in concanavalin A, plastocyanin, y-crys- ,(3pleated sheets that are packed together. We show, on the left tallin, superoxide dismutase, prealbumin, and the immunoglobin ofthe figures, two hypothetical untwisted (3-sheets packed with fragment VREI. This model shows how the observed relative ori- their rows of side chains aligned: those in the top (-sheet are entation of two packed (3-sheets is a consequence of (i) the rows parallel to those in the bottom. On the right of the figures we of side chains at the interface being approximately aligned and show what happens when these packed (3-sheets are twisted (ii) the (3-sheet having a right-handed twist. The special amino acid about an axis that is in the plane oftheir interface. We see that composition ofresidues at the (-sheet-to-(3-sheet interfaces makes for the twisted close-packed (3-sheets: (i) The ends of the side the contact surfaces essentially smooth and hydrophobic. chains that form contacts across the interface maintain their alignment. (ii) The main chains of the two sheets now point in The three-dimensional structure of most globular proteins can different directions. be described as an assembly of close-packed a-helices and (& As one looks down the twist axis, the main chains ofthe top pleated sheets. It is therefore important to understand the rules ,(3sheet go from left to right, while those ofthe bottom go from that govern the packing ofsecondary structure (1-3). We have right to left (Fig. 2b). As one looks from the top (Fig. 2c), the previously analyzed the packing ofa-helices on a-helices (4) and main chains make an angle, which is negative because it rep- on (3-sheets (5). In this paper, we concentrate on (3sheet-to-,(- resents a left-handed screw rotation. This angle, fQ, would be sheet packing in a family ofproteins that are formed by two (3- -350 if the top and bottom main chains are 10 A apart and the pleated sheets packed face to face. twist along the chains is 40/A. Concanavalin A (6), plastocyanin (7), 'y-crystallin (8), super- This angle of -35° would be increased or decreased by the oxide dismutase (9), prealbumin (10), and the immunoglobulin rows of residues being not exactly aligned, by there being a domains (11) are representative members of this family, which different amount of twist, or both. If the side chains are not also contains the coat proteins of tomato bushy stunt virus (12) exactly aligned, and if the direction ofthe twist axis is closer to and of southern bean mosaic virus (13), azurin (14), and other the direction of the strands in one (-sheet than to that in the proteins. All these proteins have two (8-pleated sheets packed other, the extent of the twist in the two (3-sheets will differ face to face and oriented so that the direction of the strands in somewhat. one sheet is at an angle ofabout -300 to that in the other sheet, Viewed from the end, the twisted (3-pleated sheets in pro- the minus sign indicating a left-handed screw rotation (Fig. 1). jection take a cylindrical shape that Fig. 2b shows clearly. Note We show here that this characteristic orientation is a natural that the "barrel effect" (17) is observed even in the absence of consequence of the right-handed twist of normal (pleated a continuous network of hydrogen bonds joining the two (3- sheets and allows the close packing of side chains between the sheets into a single one. In our model, top and bottom strands two (3sheets in contact. In other proteins formed by (3pleated have their side chains pointing to each other and their main sheets, such as trypsin or staphylococcal nuclease, the (3-pleated chains cannot hydrogen bond. The actual shape ofthe structure sheets are packed with the strand directions making an angle is not a "barrel" or a cylinder, but a twisted prism with a rec- ofabout 900 (1). The principles applying to these structures are tangular cross-section that rotates around the twist axis. different and will be discussed elsewhere. The model described here supersedes a previous model of A model for pacldng twisted (3-pleated sheets Chothia et al. (1). In the remainder ofthe paper, we shall discuss The P-pleated sheets observed in protein structures are not flat its relevance to real protein structures. but twisted in a right-handed direction (16). In this section we describe the effects of introducing this twist into an idealized ,B-Sheet-to-p-sheet packing in six proteins model of two (3-sheets packed face to face (Fig. 2). This model We used computer graphics to examine the detailed atomic will be useful in understanding the structural descriptions pre- structures of the six proteins or protein subunits illustrated in sented in later sections. Fig. 1: concanavalin A, plastocyanin, y-crystallin domain I, su- Fig. 2a illustrates one effect of the right-handed twist on a peroxide dismutase, prealbumin, and immunoglobulin frag- single polypeptide chain. On twisting ofthe main chain, the side ment VREI. For each protein, we determined the twist and the chains that point up curve in the opposite direction to those that relative orientation ofthe (B-sheets and we analyzed the packing point down. As one looks down the chain, those that point up of amino acid residues at the (3-sheet to (3-sheet interfaces. P-Sheet Twist. The twist is conveniently expressed by the The publication costs ofthis article were defrayed in part by page charge dihedral angle between pairs of adjacent strands. This angle is payment. This article must therefore be hereby marked "advertise- negative for all but three of44 pairs ofstrands in the twelve (& ment" in accordance with 18 U. S. C. §1734 solely to indicate this fact. sheets, indicating a normal right-handed twist of the strands, 4146 Downloaded by guest on October 1, 2021 Biochemistry: Chothia and janin Proc. Natl. Acad. Sci. USA 78 (1981) 4147 7 2S 1472 747 2 & 243~~~S C 2 042A 38 57 PIG e-Cry r S3 Sod Pro VREI FIG. 1. The 3-pleated sheets in concanavalin A (Con A), plastocyanin (Pla), y-crystallin (-,Cry), superoxide dismutase (Sod), prealbumin (Pra), and the immunoglobulin fragment VREI. *, Ca atoms in the "top" -3-sheet; 0, Ca atoms in the "bottom" 3sheet. Atomic coordinates are from the Cambridge Protein Data Bank (15), except for plastocyanin and 'tycrystallin, gifts of J. M. Guss, H. C. Freeman, and T. Blundell (7, 8). which leads to a left-handed twist of the 3-sheets viewed from middle, and the sections in Fig. 4c, through the back. A com- the edge. The mean ofthe distribution (Fig. 3) is -17° and the plete representation of the structures would involve stacking standard deviation is 9°. The distribution is not significantly a number of such sections on top of each other. different from that found in a/P proteins, in which the mean We see in Fig. 4 that: (i) The description of the prealbumin dihedral angle between adjacent strands is - 19° with a standard and VREI structures as made oftwo ,(3pleated sheets packed face deviation of 70 (4). to face is essentially correct. Residues not belonging to the (3 The dihedral angle between the right-most and left-most sheets are marked in dotted lines. They make little contribution strands of each (3-sheet is a measure of its total twist. It varies to the internal packing. (ii) The (3sheet-to-,3sheet interface is between -30° over six strands in the top (-sheet of concanav- made up of side chains pointing directly to each other. In each alin A and -65° over four strands for the top (3-sheet of preal- section, a line may be drawn that separates one (3-sheet from narrow distribution the other. Side chains from either side hardly cross this line. bumin (Table 1). Thus, despite the rather Thus, intercalation of side chain from top and bottom is the in Fig. 3, the (3-sheets can differ widely in their total twist. exception rather than the rule in these interfaces. In the six Relative Orientation of the (Sheets. Relative orientation sections shown, it occurs once with Trp-35 in VREI (Fig. 4b), is fixed by the 0 angle of Fig. 2c. The values found for the six which fits its side chain into a hole in the bottom (3-sheet. Yet, proteins are listed in Table 1. The values are in the range -30° the interface is not a plane. Due to the twist, the dividing line + 150.
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