"Is alpha-keratin a coiled coil?"

Date:: 1952

Reference:: PP/CRI/I/1/1

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

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$NATURE—-No 880—CORRES—ÜRÖEKT Is a-Keratin a Coiled Coil ? All recent work 1- has confirmed tliat the structure of the synthetic polypeptide poly-iyvinethyl -l -glut- amate is based on the a-helix of Pavíling and Corey'. This structure gives a strong 1-5-A. reflexion on the meridian, and both McArthur 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. 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 ai\ insuperable objection, since the a-helix might be more tiglifey coiled';' 'but - it is difficult to see how one could'obtain such a narrow meridional arc as is observed for a-keratin, even allowing for our ignorance of ine 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 Trnsst likely general solution is that thé a-helix is bent ' ' super-helix, or coiled-coil. If the a-heli'i if into a supi ts projection < tion in density at intervals of 5-t cos io ^ _ 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 lO-J 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) th£ forces prevent ing small rotations about single Taonds 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), the average energy per residue to deform the a-helix by the amount described above isgxbout 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, bj.it resists large daiirmations. So far, no reason has been giv£n 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-heliees. . * I should like to suggest that ther^ 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 tÄe 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 intp 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 t 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 thèse two ideas lead to a coiled-coil which may explain some of the datá 1 better than a straight a-helix. F. H. C. Crick Medical Research Couhcil Unit for the Study of the Molecular Structure of Biological Systems, Cavendish Laboratory, Cambridge. Oct. 22.$

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