Abstract
The dissection of the activities mediated by type I collagen requires an approach by which the influence of triple-helical conformation can be evaluated. The alpha 1 beta 1 and alpha 2 beta 1 integrin binding sites within type I collagen are dependent upon triple-helical conformation and contained within residues 14-822 from alpha 1(I). Seven alpha 1(I)-derived triple-helical peptides (THPs) were synthesized based on charge clustering (alpha 1(I)256-270, alpha 1(I)385-396, alpha 1(I)406-417, alpha 1(I)415-423, alpha 1(I)448-456, alpha 1(I)496-507, and alpha 1(I)526-537). Three additional THPs were synthesized (alpha 1(I)85-96, alpha 1(I)433-441, and alpha 1(I)772-786) based on previously described or proposed activities (Kleinman, H. K., McGoodwin, E.B., Martin, G. R., Klebe, R. J., Fietzek, P. P., and Wooley, D. E. (1978) J. Biol. Chem. 253, 5642-5646; Staatz, W. D., Foik, K. F., Zutter, M. M., Adams, S. P., Rodriquez, B. A., and Santoro, S. A. (1991) J. Biol. Chem. 266, 7363-7367; San Antonio, J. D., Lander, A. D., Karnovsky, M. J., and Slayter, H. S. (1994) J. Cell Biol. 125, 1179-1188). Of the ten THPs, alpha 1(I)772-786 THP had the greatest activity, with half-maximal normal dermal fibroblast adhesion occurring at a peptide concentration of 1.6 microM. Triple-helicity was essential for activity of this sequence, as the non-triple-helical peptide analog (alpha 1(I)772-786 SSP) exhibited considerably lower levels of cell adhesion promotion even at peptide concentrations as high as 100 microM. Within the sequence itself, residues 784-786 (Gly-Leu-Hyp) were important for cellular recognition, as the alpha 1(I)772-783 THP had greatly reduced cell adhesion activity compared with alpha 1(I)772-786 THP. Preliminary studies indicate that the beta 1 integrin subunit mediates fibroblast adhesion to alpha 1(I)772-786 THP. The identification of fibroblast integrin binding sites within type I collagen may have important implications for understanding collagen metabolism.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
