Is a-Keratin a Coiled Coil ? ALL recent work!~* has confirmed that the structure of the synthetic polypeptide poly-y-methyl-r-glut- amate is based on the a-helix of Pauling and Corey’. This structure gives a strong 1-5-A. reflexion on the meridian, and both MacArthur® and Peruts' have shown that this reflexion also occurs in «-keratin. This suggests forcibly that the «-helix forms sn important part of a-keratin. No. 4334 November 22, 1952 ‘There are certain difficulties in this idea. One of the main features of «-keratin is the strong reflexion at 5-15A. on, or very close to, the meridian. The normal a-helix gives strong reflexions on the 5:4-A. layer line, but displaced from the meridian, The difference in spacing is not an insuperable objection, since the a-helix might be more tightly coiled; but it is difficult to see how one could obtain such a narrow meridional are as is observed for a-keratin, even allowing for our ignorance of the details of the side-chain arrangement. One way to bring the reflexion nearer to the mer- idian would be to tilt the a-helix. Since the a-keratin pattern is of wide occurrence, one would expect the tilt to be a constant feature of the structure. The most likely general solution is that the a-helix is bent into & super-helix, or coiled-coil. If the a-helix is twisted into a super-helix with a pitch angle of about 18°, its projection on to the axis would have a periodic variation in density at intervals of 5:4 cos 18° ~ 5-1 A., and so might explain the chserved meridional reflexion which co nds to this spacing. A pitch angle of 18° could be obtained, for example, from a super-helix of radius 10} A. (the probable distance between helices) and axial spacing 198 A. (the repeat of African porcupine quill)’, It is possible to make a rough estimate of the energy required to deform the «-helix by this amount by assuming that (1) the forces prevent- ing small rotations about single bonds are small ; (2) the hydrogen bond can be fairly easily deformed by small amounts in direction ; (3) the main restoring force comes from the resistance of the hydrogen bonds to deformation in length. ing a force constant for a hydrogen bond of, say, 3 X 10* dynes/cm. (see, for example, Davies"*), the average energy per residue to deform the a-helix by the amount described above is about one-tenth of a kilo-calorie per residue, which is small. This energy increases roughly as the fourth power of the pitch angle, so that the a-helix can easily be bent through small angles, but resists large deformations. So far, no reason has been given why the «-helix should be deformed. It seems probable that this is due to the difficulty of fitting together the side-chains of two adjacent a-helices. I should like to suggest that there may be a general plan underlying the detailed packing of all the various side-chains found in proteins. If the side-chains of the «-helix are thought of schematically as knobs on the surface of a cylinder, then it is found that the pattern on this surface consists of knobs alternating with ‘holes’, that is, spaces into which the knobs from a neighbouring «-helix could fit. The position of these holes is roughly independent of the exact nature of the surrounding side-chains. In poly-y-methyl]-t-glutamate, the side-chains are long and flexible and they can reach out towards the nearest hole without deforming the a-helix. In pro- teins, on the other hand, the side-chains are, on the average, smaller and leas flexible, and neighbouring helices are nearer together (10}A. compared with 12 A. for poly-y-methyl-z-glutamate). It is therefore not unreasonable to simplify the undoubtedly com- plicated packing of side-chains into a set of standard rigid knobs fitting into standard holes. “t is impossible to pack such models of the a-helix closely side by side, since a good fit in one place. produces a bad fit somewhere else, due to the non- in 1 nature of the helix. However, it can be shown that by deforming the helices into coiled-coils NATURE 883 the knobe can be made to interlock systematically. The energy for deforming the helices could come from the closer fitting together of the side-chains. The objects of this communication are to stress that the c-helix can be deformed an appreciable amount if the deformation is systematic, to suggest that there may be a general plan underlying the pack- ing together of side-chains, and to show that theee two ideas lead to a coiled-coil which may explain some of the data" better than a straight «-helix. F. H. C. Crick Medical Research Council Unit for Research on the Molecular Structure of Biological Systems, Cavendish Laboratory, Cambridge. Oct. 22. ‘ Perutz, M. F., Nature, 167, 1053 (1951). * Cochran, W., and Crick, F. H. C., Nature, 169, 234 (1952). * Samford, C. H., Brown, L., Ellfott, A., Hanby, W. E., and Trotter, 1. F., Nature, 169, 357 (1952). “ Yakel, H. L., Pauling, L., and Corey, B. B., Nature, 168, 920 (1952). * Fraser, H. D. B., and Price, W. C., Nature, 120, 490 (1952). * Cochran, W., Crick, F. H. C., and Vand, V., Acta Cryst., 5, 581 * Panes, L., and Corey, R. B., Proc. U.S. Nat. Acad, Set., $7, 241 MacArthur, I., Nature, 189, 38 (1943), * Rear, R. 8, J. Amer. Chem. Soe., 65, 1784 (1943). 1© Davies, M., Ann. Kep. Chem. Soc., 43, 1 (1946), 11 Crick, F, H. C., Acta Cryst., 6, 381 (1952).