Altroff, H. and Schlinkert, R. and Van Der Walle, C.F. and Bernini, A. and Campbell, I.D. and Werner, J.M. and Mardon, H.J. (2004) Interdomain tilt angle determines integrin-dependent function of the ninth and tenth fIII domains of human fibronectin. Journal of Biological Chemistry, 279. pp. 5995-6003. ISSN 0021-9258Full text not available in this repository. (Request a copy from the Strathclyde author)
Integrins are an important family of signaling receptors that mediate diverse cellular processes. The binding of the abundant extracellular matrix ligand fibronectin to integrins α5β1 and αvβ3 is known to depend upon the Arg-Gly-Asp (RGD) motif on the tenth fibronectin FIII domain. The adjacent ninth FIII domain provides a synergistic effect on RGD-mediated integrin α5β1 binding and downstream function. The precise molecular basis of this synergy remains elusive. Here we have dissected further the function of FIII9 in integrin binding by analyzing the biological activity of the FIII9-10 interdomain interface variants and by determining their structural and dynamic properties in solution. We demonstrate that the contribution of FIII9 to both α5β1 and αvβ3 binding and downstream function critically depends upon the interdomain tilt between the FIII9 and FIII10 domains. Our data suggest that modulation of integrin binding by FIII9 may arise in part from its steric properties that determine accessibility of the RGD motif. These findings have wider implications for mechanisms of integrin-ligand binding in the physiological context.
|Keywords:||human fibronectin , signaling receptors , fibronectin , Pharmacy and materia medica, Biochemistry, Cell Biology, Molecular Biology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||22 Feb 2012 14:38|
|Last modified:||06 Jan 2017 06:23|