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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 1931年，阿斯特伯里勋爵首次获得了硬角蛋白的衍射图。从那时起，已经发表了300多篇论文，提出了可能的分子排列和结构。对这种结构的解决将是科学发现的重大突破。到目前为止，只有Feughelman和James（2，3，4）提出的模型满足所有已知的实验数据。 该模型基于从BioCAT光束线获得的非常丰富的衍射图案。 我们的模型开始于由角蛋白螺旋形成的紧密缠绕的螺旋异二聚体。这些二聚体中的两个以紧密螺旋缠绕形成四聚体，并且8个四聚体的交错阵列以缓慢螺旋缠绕形成中间丝（IF）。这种交错使得在每360 ° X中提供六个交联，从而提供如在电子显微镜中看到的六边形阵列。这个阵列的高度复杂的衍射图案产生了一个超晶格，有6个晶格叠加，两个隐藏。这些结果是在体内获得的，我们提出的模型需要一个平行阵列的相邻对的双链卷曲螺旋分子在中间丝。 法国和瑞士科学家对体外角蛋白的研究结果表明，角蛋白的构象具有反平行性。虽然不能假设漂浮在流体中的分子会采取与纤维中受约束的分子相同的构象，但科学界仍然对这一争议存在分歧。 该项目旨在一劳永逸地消除这一争议，使用衍射数据的研究提出调查（a）之间的角度的IF和纤维的长度;（B）非常详细的中心间距的IF和半径的所有圆柱形结构的参与（c）IF直径的变化与膨胀和加热。 如果结果如预期的那样，他们将提供足够的证据来声称角蛋白的真实结构，并实现这一重大突破。

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.