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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Fields, G. B. Guy, C. A. Sweeney, S. M. San Antonio, J. D. |
| Description | Author Affiliation: Sweeney SM ( Department of Medicine and the Cardeza Foundation for Hematologic Research, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.); |
| Abstract | Cell surface heparan sulfate proteoglycan (HSPG) interactions with type I collagen may be a ubiquitous cell adhesion mechanism. However, the HSPG binding sites on type I collagen are unknown. Previously we mapped heparin binding to the vicinity of the type I collagen N terminus by electron microscopy. The present study has identified type I collagen sequences used for heparin binding and endothelial cell-collagen interactions. Using affinity coelectrophoresis, we found heparin to bind as follows: to type I collagen with high affinity (Kd approximately 150 nM); triple-helical peptides (THPs) including the basic N-terminal sequence alpha1(I)87-92, KGHRGF, with intermediate affinities (Kd approximately 2 microM); and THPs including other collagenous sequences, or single-stranded sequences, negligibly (Kd >> 10 microM). Thus, heparin-type I collagen binding likely relies on an N-terminal basic triple-helical domain represented once within each monomer, and at multiple sites within fibrils. We next defined the features of type I collagen necessary for angiogenesis in a system in which type I collagen and heparin rapidly induce endothelial tube formation in vitro. When peptides, denatured or monomeric type I collagen, or type V collagen was substituted for type I collagen, no tubes formed. However, when peptides and type I collagen were tested together, only the most heparin-avid THPs inhibited tube formation, likely by influencing cell interactions with collagen-heparin complexes. Thus, induction of endothelial tube morphogenesis by type I collagen may depend upon its triple-helical and fibrillar conformations and on the N-terminal heparin-binding site identified here. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 13 |
| Volume Number | 95 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1998-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Collagen Metabolism Endothelium, Vascular Heparin Amino Acid Sequence Cells, Cultured Chemistry Molecular Mimicry Molecular Sequence Data Protein Binding Protein Conformation Surface Properties Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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