Candidate cell and matrix interaction domains on the collagen fibril, the predominant protein of vertebrates.
Type I collagen, the predominant protein of vertebrates, polymerizes with type III and V collagens and non-collagenous molecules into large cable-like fibrils, yet how the fibril interacts with cells and other binding partners remains poorly understood. To help reveal insights into the collagen structure-function relationship, a data base was assembled including hundreds of type I collagen ligand binding sites and mutations on a two-dimensional model of the fibril. Visual examination of the distribution of functional sites, and statistical analysis of mutation distributions on the fibril suggest it is organized into two domains. The "cell interaction domain" is proposed to regulate dynamic aspects of collagen biology, including integrin-mediated cell interactions and fibril remodeling. The "matrix interaction domain" may assume a structural role, mediating collagen cross-linking, proteoglycan interactions, and tissue mineralization. Molecular modeling was used to superimpose the positions of functional sites and mutations from the two-dimensional fibril map onto a three-dimensional x-ray diffraction structure of the collagen microfibril in situ, indicating the existence of domains in the native fibril. Sequence searches revealed that major fibril domain elements are conserved in type I collagens through evolution and in the type II/XI collagen fibril predominant in cartilage. Moreover, the fibril domain model provides potential insights into the genotype-phenotype relationship for several classes of human connective tissue diseases, mechanisms of integrin clustering by fibrils, the polarity of fibril assembly, heterotypic fibril function, and connective tissue pathology in diabetes and aging.
Published In/Presented At
Sweeney, S. M., Orgel, J. P., Fertala, A., McAuliffe, J. D., Turner, K. R., Di Lullo, G. A., Chen, S., Antipova, O., Perumal, S., Ala-Kokko, L., Forlino, A., Cabral, W. A., Barnes, A. M., Marini, J. C., & San Antonio, J. D. (2008). Candidate cell and matrix interaction domains on the collagen fibril, the predominant protein of vertebrates. The Journal of biological chemistry, 283(30), 21187–21197. https://doi.org/10.1074/jbc.M709319200
Medicine and Health Sciences
Department of Pathology and Laboratory Medicine