This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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| Yazdi, Aliakbar Khalili; Vezina, Grant C; Shilton, Brian H (2017) An alternate mode of oligomerization for E. coli SecA. Sci Rep 7:11747 |
| Sullivan, Brendan; Robison, Gregory; Pushkar, Yulia et al. (2017) Copper accumulation in rodent brain astrocytes: A species difference. J Trace Elem Med Biol 39:6-13 |
| Morris, Martha Clare (2016) Nutrition and risk of dementia: overview and methodological issues. Ann N Y Acad Sci 1367:31-7 |
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| Gelfand, Paul; Smith, Randy J; Stavitski, Eli et al. (2015) Characterization of Protein Structural Changes in Living Cells Using Time-Lapsed FTIR Imaging. Anal Chem 87:6025-31 |
| Liang, Wenguang G; Ren, Min; Zhao, Fan et al. (2015) Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol 427:1345-1358 |
| Zhou, Hao; Li, Shangyang; Badger, John et al. (2015) Modulation of HIV protease flexibility by the T80N mutation. Proteins 83:1929-39 |
| Nobrega, R Paul; Arora, Karunesh; Kathuria, Sagar V et al. (2014) Modulation of frustration in folding by sequence permutation. Proc Natl Acad Sci U S A 111:10562-7 |
| Jiao, Lianying; Ouyang, Songying; Shaw, Neil et al. (2014) Mechanism of the Rpn13-induced activation of Uch37. Protein Cell 5:616-30 |
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