W0435

The Molecular Structure of Collagen: Developing the Science of Fibre Crystallography. Orgel, J¹. Irving, T². Miller, A³. Wess, T³., ¹Dept. of Biochemistry, Finch Univ. of Health Sciences/Chicago Medical School, 3333 Greenbay Rd., North Chicago, IL 60064, ²CSRRI, Dept. BCPS, Illinois Inst. of Technology, 3101 S. Dearborn, Chicago IL 60616, ³Inst. of Biological Sciences, Univ. of Stirling, Stirling, FK9 4LA Scotland.

The most abundant collagen, type I, readily forms fibrils that convey the principal mechanical support and structural organization of connective tissues such as: tendon, skin, bone, ligaments, lung, cornea, and vasculature. A molecular level model of the supermolecular structure of collagen, derived via Multiple Isomorphus Replacement and obtained from the intact tissue will be presented here.

Because of its great abundance and principal role in connective tissue, the molecular structure of type I collagen has been actively sought after for many years. Most of these efforts have been of limited success due to the profound difficulties involved in obtaining sufficiently high resolution, unambiguous data. One of the major frustrations has been due to the difficulty of utilizing the intrinsic advantage of fibre diffraction over other techniques; that the molecules can be maintained in their native state whilst detailed molecular information is ascertained. In recent years, the Orgel lab has developed a means for solving this problem using techniques more commonly associated with single crystal crystallography, and is now working to refine the model of the protein structure. This model is based exclusively on the electron density calculated from data from native samples.

Collagen chains are believed to contain intermolecular binding and recognition sites for other macromolecules, including other collagen types that are used to interconnect the scaffolding network of the cell. This network (as part of the extracellular matrix) maintains cell shape, spatial location, and surface to surface contact with neighboring cells. The orientation of collagen fibrils and the packing arrangement of the collagen molecules and hence the fibrils impact the properties of the tissue in question, be that to create the transparent nature of the mammalian eye, the elasticity of skin, or the strength and integrity of bone. Refinement of the native collagen structure will undoubtedly reveal likely sites for intermolecular contacts, and how the packing structure affects the properties of connective tissue.