The in situ supermolecular structure of type I collagen

Background: The proteins belonging to the collagen family are ubiquitous th roughout the animal kingdom. The most abundant collagen, type 1, readily fo rms fibrils that convey the principal mechanical support and structural org anization in the extracellular matrix of connective tissues such as bone, s kin, tendon, and vasculature. An understanding of the molecular arrangement of collagen in fibrils is essential since it relates molecular interaction s to the mechanical strength of fibrous tissues and may reveal the underlyi ng molecular pathology of numerous connective tissue diseases. Results: Using synchrotron radiation, we have conducted a study of the nati ve fibril structure at anisotropic resolution (5.4 Angstrom axial and 10 An gstrom lateral). The intensities of the tendon X-ray diffraction pattern th at arise from the lateral packing (three-dimensional arrangement) of collag en molecules were measured by using a method analogous to Rietveld methods in powder crystallography and to the separation of closely spaced peaks In Laue diffraction patterns. These were then used to determine the packing st ructure of collagen by MIR. Conclusions: Our electron density map is the first obtained from a natural fiber using these techniques (more commonly applied to single crystal cryst allography). It reveals the three-dimensional molecular packing arrangement of type I Collagen and conclusively proves that the molecules are arranged on a quasihexagonal lattice. The molecular segments that contain the telop eptides (central to the function of collagen fibrils in health and disease) have been identified, revealing that they form a corrugated arrangement of crosslinked molecules that strengthen and stabilize the native fibril.