THE MOLECULAR STRUCTURE OF COLLAGEN TYPES I AND II

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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. The fibrous collagens are amongst the most important structural proteins known to man. They are ubiquitous in nature and form the structural basis of various organ tissues as well as vasculature, skin, bones and cartilage. The major collagen types, the fibrillar forms, behave as scaffolding, a three dimensional network with (as yet) structurally ill-defined binding and recognition sites for numerous extracellular matrix macromolecules. Yet relatively little is understood regarding collagens molecular arrangement. Such knowledge will provide critical insights into key biological processes in development, growth, repair and disease. Type I collagen is the single most abundant collagen in the animal kingdom and a critical part of most mammalian connective tissues. Type II collagen is a crucial component of mammalian cartilage, inter-vertebral discs and other tissues during their development, yet relatively little is known concerning the organization of these two collagen types at the sub-fibrillar level. Fortunately, the fibrillar type I and II collagen's found within rat tail tendon and in lamprey tissues are somewhat crystalline, a property that will allow an investigation of collagen molecular structure through X-ray fiber diffraction. Diffraction patterns obtained from both rat tail tendon and several lamprey tissues contain information regarding the sub-fibrillar organization of collagen chains, the specific level of interest to this study. Previously, such data (collected at BioCAT) was used to solve the 3D structure of type I collagen to 1.1 nm, revealing important constraints on the mechanism by which collagenase (and other EM active molecules) bind the collagen chains. Subsequent developments in cryo-freazing techniques will be used to extend the resolution of this structure, whilst data is collected for type II collagen using the newly developed micro-focus capabilities of the BioCAT beamline to similarly solve its structure using MIR.