SOLUTION FOR THE CONTROVERSY ABOUT THE STRUCTURE OF HARD ALPHA-KERATIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lord Astbury obtained the first diffraction patterns of hard ¿¿-keratin in 19311. Since that time over 300 papers have been published proposing possible molecular arrangements and structures. The solution to this structure would be a major break through in scientific discovery. To date only the model proposed by Feughelman and James(2,3,4) satisfies all known experimental data. This model was based on the very rich diffraction patterns obtained from the BioCAT beamline. Our model starts with a tightly wound helical heterodimer formed by ¿¿¿¿¿nand ¿¿¿¿¿nkeratin helices. Two of these dimers wind in a tight helix to form a tetramer and a staggered array of 8 tetramers wind in a slow helix to form the intermediate filaments (IFs). The stagger is such as to provide six cross links in every 360¿X thus providing the hexagonal array as seen in electron microscopy. The highly complex diffraction pattern from this array gives rise to a superlattice, with 6 lattices superimposed, two hidden. These results were obtained in vivo and our proposed model requires a parallel array of neighbouring pairs of the two-chain coiled-coil molecules in the intermediate filaments. Results from studies of in-vitro ¿¿¿{keratin by French and Swiss scientists have revealed anti-parallelism5 in their conformation. Whilst it is not to be assumed that a molecule floating in a fluid will adopt the same conformation as one under constraint in a fibre, the scientific world still stands divided on this controversy. This project aims to dispel this controversy once and for all using diffraction data from the studies proposed to investigate (a) the angle between the IF and the length of the fibre;(b) very detailed centre to centre spacings of the IFs and the radii of all cylindrical structure involved (c) IF diameter changes with swelling and heating. If the results are as expected, they will provide sufficient proof to claim the true structure of keratin and achieve this major break-through.