"Is alpha-keratin a coiled coil?"

Date:
1952
Reference:
PP/CRI/I/1/1
Catalogue details

Licence: In copyright

Credit: "Is alpha-keratin a coiled coil?". Source: Wellcome Collection.

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    no. 4334 November 22, 1952 NATURE There are certain difficulties in this idea. One of the main features of a-keratin is the strong reflexion at 5-15 A. 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 is difficult to see how one could obtain such a rrow meridional arc 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 a 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 observed meridional reflexion which corresponds 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) 8 ' 9 . It is possible to make a rough estimate of the energy required to deform the a-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. Assuming a force constant for a hydrogen bond of, say, 3 X 10 4 dynes/cm. (see, for example, Davies 10 ), 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 a-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 a-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 a-helix could fit. The position of these holes is roughly independent of the exact nature of the surrounding side-chains. In poly-y-methyl -l -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 less flexible, and neighbouring helices are nearer together (10£ A. compared with 12 A. for poly-y-methyl-L-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. It 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- integral nature of the helix. However, it can be shown that by deforming the helices into coiled-coils the knobs 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 a-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 these two ideas lead to a coiled-coil which may explain some of the data 11 better than a straight a-helix. F. H. C. Crick Medical Research Council Unit for Research on the Molecular Structure of Biological Systems, Cavendish Laboratory, Cambridge. Oct. 22. 1 Perutz, M. F., Nature, 167, 1053 (1951). 2 Cochran, W., and Crick, F. H. C., Nature, 169, 234 (1952). 3 Bamford, C. H., Brown, L„ Elliott, A., Hanby, W. E., and Trotter, i. F., Nature, 169, 357 (1952). 4 Yakel, H. X., Pauling, L., and Corey, B. B., Nature, 169, 920 (1952). 5 Fraser, B. D. B„ and Price, W. C., Nature, 170, 490 (1952). •Cochran, W., Crick, F. H. C., and Vand, V., Acta Cryst., 5, 581 (1952). ' Pauling, L., and Corey, B. B., Proe. U.S. Nat. Acad. Sci., 37, 241 (1951). 8 MacArthur, I., Nature, 152, 38 (1943). 9 Bear, B. 8., J. Amer. Chem. Soc., 65, 1784 (1943). 10 Davies, M„ Ann. Bep. Chem. Soc., 43, 1 (1946). 11 Crick, F. H. C., Acta Cryst., 5» 381 (1952). Is a -Keratin a Coiled Coil ? All recent work 1-6 has confirmed that the structure of the synthetic polypeptide poly -y -methyl -l -glut- amate is based on the a-helix of Pauling and Corey 7 . This structure gives a strong 1 -5-A. reflexion on the meridian, and both MacArthur 8 and Perutz 1 have shown that this reflexion also occurs in a-keratin. This suggests forcibly that the a-helix forms an important part of a-keratin. the attached cutting Troni our issue' for ?.. WOV 19S?