George Gorin Oklahoma State University Stillwater
Models of the Polypeptide a-Helix and of Protein Molecules
This paper describes two types of molecular models which may be found useful in the study of protein structure. The first type consists of commercially available ball-and-stick models with some modifications; these models have been used to represent the a-helix structure proposed for polypeptide chains by Pauling, Corey, and Rranson (1,2). I n the second type of model, a-helical structures are represented by cylindrical tubes, and their use has been exemplified by the representation of a structure for insulin proposed in 19,55 by Lindley and Rollett (5). Atom models for constructing polypeptide chains have been described by Corey and Pauling (4) and by Lindley and Rollett (5); these models represent interatomic distances and angles quite precisely, but producing such models requires a considerable investment of time and money. The models described in this paper are easily made a t very moderate cost; although less precise than those just mentioned (3, 41, they should prove adequate for representing much of the information concerning proteiu structure which is now being accumulated.
Figure 1. Phdagraph of the a-helix model. H atoms are light, C=O atoms can be e o d y recognized for they ore connected b y springs; the N-H O:Ciudaporiti>ncanfirrt bereen with the fifth corbonyl group from the left.
The a-helix is f o r m ~ dwhen a polypeptide chain coils into a spiral so that the K-H group becomes hydrogenbonded to the fourth C=O group following it in the chain. The helix can be right- or left-handed (i.e., spiral clockwise or counterclockwise, respectively, from the carhoxyl end). Small variations in hond angles will cause the structure t o repeat after 11, 14, or 18 residues (I). While there is as yet no evidence that one of these possibilities is uniquely favored, most attention has been accorded t o the 18-:esidue, 5-turn helix, in which the repeating unit is 27 A long. Diagrams of the a-helix can he found in many publications; an especially clear schematic diagram of the helix dimensions is given in an article by Corey and Pauling and in a book by Scheraga (5). 44
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A photograph of the model of the a-helix is shown in Figure 1. The basic materials for constructing the model were provided by three sets of E. H. Sargent and Company "Molecular Models" (Catalogue 109, S61815). The models of carbon atoms (black), hydrogen (yellow), and oxygen (red) were used without modification. Models of the nitrogeu atoms were made from hydrogen atoms (which are supplied in sufficient number for the purpose) by drilling two additional holes a t 120' angles. The procedure used in drilling the holes is illustrated and explained in Figure 2. The nitrogen atom models were painted blue so they
Figure 2. Procedure for making nitrogen otom models. Drill o 'frin. hole in o wooden block at o 30- angle with the wrfoce. Center hydrogen atom model under drill or shown. Clamp block to drill plotform and make hole. Insert dowel in newly mode hole and repeal to make the third hole.
would show up dark in the black-and-white photograph. The R groups were represented hy single-holed atom models which were painted green to provide appropriate contrast in the photographic reproduction. The sticks and springs used to connect the atom models were cnt, and the models assembled, t o the scale 3 cm = 1 A, i.e., distances between the centers of the atom models were as follows (6, 7): X-C and C-C, 4.5 em; C(=O)NH, 4.0 cm; C-H and X-H, 3.1 cm; C=O, 3.7 em. A 30-inch piece of 0.5-in. aluminun~rod was used for mounting. To assemble the helix, the amino acid models were connected and adjusted so as to bring the appropriate N-H. . .O=C groups as close as possible to the correct relative position. Then, four appropriately placed connecting sticks were fastened to the rod with thin bolts and nuts; ooce fastened, the model was quite rigid, and could he moved freely without danger of disrupting the arrangement. Owing to inaccuracies in the bond lengths and angles, the distance between the hydroge~l-bonded oxygen and nitrogen atoms was not precisely uniform, but the deviation from the calculated value (2.86 A, 8.6 cm; this is somewhat longer than the preferred hydrogen bond distance of 2.79 (1, 2)) could be kept under 15% and averaged less than this. The model shown in the photograph comprises 12 amino acid residues, which make a little more than three turns, and the length of the model conforms very closely to the correct value.
Inspection of the a-helix model reveals that the spiralling polypeptide chain forms a compact cylindrical core, from which there protrnde the hydrogen atoms and R groups attached t o the a-carbon atoms. Illsofar as the individual character and function of proteius are concerned, the polypeptide core is of little consequence, while the nature and relative location of the R groups are of pre-eminent importance. This suggested the idea of making protein models which represent the latter characteristic without the necessity of asse~nhling the helix. Figure 3 portrays an example of this type of model.
Figure 3.
M o d e l o f a structure for insulin propared b y Lindley ond Rollett 131.
111the lower part of the photograph are s l ~ o ~ vthe n amino-acid sequences in what have been called the Aaud B-chains. Lindley and Rollett (3) suggested that the R chain might be a simple right-handed a-helix, except for a distortion a t position 28, due to the fact that the prolyl residue cannot fit into the a-helix. 111chain A, it was suggested that the conformation from 12-21 to A-10 might also he a right-handed a-helix, and that there would be an inversion of the sense of the helix a t A-9, making it possible for the cysteinyl residues a t A-11 and A-6 to be joined by an S-S bond. The axes of the right- and left-handed helical parts form a 30 angle. h 2-in. lucite tube, 18.5 in. loug, was used t o represent the B-chain. I t was nlounted in a drill press and a small hole made 1.50 em fmm one end. Then the tnbe was advanced 1 3 0 cm, rotated 10O0, and a secoud hole made, the process being repeated thirty timrii in all. The position of the nineteenth hole is then exactly 27.0 cm and 5 turns (1800") from the first; i.e., the location of the holes corresponds to that of the a-carbon atomsoin the 18-residue, 5-turn helix at a scale of 1 em = I A. Labels bearing the symbols of thc appropriate amino acids were affixed to the tube, their centers coinciding with the holes; the distortion a t Pro-28, which comes too near the end of the chain to have much effect on the conformation, is not represented. Siuce the C,, Co, S,and 0 atoms in the helix are located a t different distances from its axis (2.29, 1.61, 1.5!1, and 1.74 A, respectively (I)),the surfaceof the tube does uot represent the contours of the helix. The
centers of thc a-carbon atoms should he visualized as being 0.25 cm below the surface of the tube, while the van der Waals surfaces of the other atoms would protrude more or less above the surface. The center of p-carbon atoms, i.e., of the first carbon atoms in the R groups (excepting glycyl), is 3.34 A from the helix axis, and would accordingly he 0.80 cm above the surface of the tube. The p-carbon atoms would not be perpendicularly in line with the holes in the model, but the relative position of the R gronps is the same as that of the labels. It is intended that visualization of the R groups should be left, for theonlost part, to the imagination. The scale 1 cm = 1 h was deliberately chosen equal t o that of some commercially available space-filling models (Fisher-Taylor-Hirshfelder Models, Fisher Scientific Company, Catalogue 63, 12-821); these can then be used to construct a scale model of any R group of special interest. I n making the model of the A-chain, for example, two pieces of tubing, 5 in. and 9 in. long, were first cut and joined together t o form the desired 30" angle; positions A-21 to A-10 were marked wit11 the aid of a drill press in the manner already described; a model of CH1SSCH2 was constructed with the abovenamed atom models and used to locate position A-6 with respect to A-11; finally, positions A-5 to A-1 were located, each 1.50 cm and 100' from the preceding position, spiralling counterclockwise. The two tubes in the model were mounted 9.5 em apart, in accordance with Lindley and Rollett's model (5); this accommodates the other two disulfide bridges. I t had originally been intended to join the positions of the cysteinyl residues with brackets representing the CHPSSCHl bridges to scale, but this did not prove easily feasible, and was not done. Packing the helical structures to scale must, of course, be done with reference to other data than the dimensions of the tubes themselves, for the reasons discussed. Pauling and Corey ( g ) estimated, from the density of proteins, that the average diameter of the a-helix would be 10.5 A; but the cross section of the helix might he expected to vary, depending on the nature of the R groups. I t was recognized by Lindley and Rollett (5) that their suggestion was quite speculative. The contents of this paper should not be regarded as support for their views, as the only purpose is to show how this-or alternativesuggestions might he represented with models. On the hasis of recent findings, it is believed that the a-helical content of proteins may vary from considerahle to naught, and that no protein consists entirely of a-helices; in the case of insulin, no definitive conclusions have yet been published. The ease with which the models can be huilt should encourage their use in representing speculative ideas; if they should he proven wrong, little effort will have been wasted. A further economy and simplification can be effected by using 2-in. paper mailing tubes on the surface of which the symbols of the amino acids can be written directly; in this way, the model of a simple protein can he made in a few hours' time. Acknowledgment
We wish to thank Heinz Hall, John McDermed, and Bobby Franklin for assistance in constructing the models. This work was supported by Grant G-19074 from the Sational Science Foundation. Volume 41, Number I , lonuary 1964
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Literature Cited
L.,COREY,R. B., AND BRANSON, H. R., PTOC. Natl. (1) PAULING, Acad. Xci., 37, 205, 235 (1951). L., AND COREY,R. B., Fortsehr. Chem. O?g. Na(2) PAWLING, tumfoffe,11,180 (1954). H., AND ROLLETT, J. S., Biochin. Biophys. Ada, (3) LINDLEY, 18,183(1955). R. B., AND PAWLING, L., Rev. Sn'. in st^., 24, 621 (4) CUREY, (3953).
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( 5 ) COREY,R. B., A N D PAULING, L., Kend. 1st. Lombard0 Sci. Leltere, A89, 10 (1955). See also SCHERAGA, H. A,,
"Protein Structure," New York, Academic Press, 1961, p. 86. L., "The Nature of the Chemical Bond," 3rd ed., (6) PAULING, Cornell University Press, Ithaca, New York, 1960,p.498R. (7) "Tables of Interatomic Distances and Configurations in Molecules and Ions," London. The Chemical Society, 1958.
