The in situ supermolecular structure of type I collagen.
BACKGROUND
The proteins belonging to the collagen family are ubiquitous throughout the animal kingdom. The most abundant collagen, type I, readily forms fibrils that convey the principal mechanical support and structural organization in the extracellular matrix of connective tissues such as bone, skin, tendon, and vasculature. An understanding of the molecular arrangement of collagen in fibrils is essential since it relates molecular interactions to the mechanical strength of fibrous tissues and may reveal the underlying molecular pathology of numerous connective tissue diseases.


RESULTS
Using synchrotron radiation, we have conducted a study of the native fibril structure at anisotropic resolution (5.4 A axial and 10 A lateral). The intensities of the tendon X-ray diffraction pattern that arise from the lateral packing (three-dimensional arrangement) of collagen 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 structure 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 crystallography). 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 telopeptides (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.
Orgel
J P
JP
Centre for Extracellular Matrix Biology, Department of Biological Sciences, University of Stirling, FK9 4LA, Stirling, United Kingdom. jorgel@tigger.cc.uic.edu
Miller
A
A
Irving
T C
TC
Fischetti
R F
RF
Hammersley
A P
AP
Wess
T J
TJ
D024042:Collagen Type I / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods; D008958:Models, Molecular; D013499:Surface Properties; D017356:Synchrotrons; D013710:Tendons / Q000737:chemistry*
D024042:Collagen Type I