Interdomain tilt angle determines integrin-dependent function of the ninth and tenth FIII domains of human fibronectin
Altroff, H., Schlinkert, R., Walle, C.F., Bernini, A., Campbell, I.D., 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, (53), 55995-56003. (doi:10.1074/jbc.M406976200).
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Description/Abstract
Integrins are an important family of signaling receptors that mediate diverse cellular processes. The binding of the abundant extracellular matrix ligand fibronectin to integrins 51 and v3 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 51 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 51 and v3 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.
| Item Type: | Article |
|---|---|
| ISSNs: | 0021-9258 (print) |
| Related URLs: | |
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
| Divisions: | University Structure - Pre August 2011 > School of Biological Sciences |
| Item ID: | 56743 |
| Date Deposited: | 07 Aug 2008 |
| Last Modified: | 12 May 2013 01:18 |
| Contributors: | Altroff, H. (Author) Schlinkert, R. (Author) Walle, C.F. (Author) Bernini, A. (Author) Campbell, I.D. (Author) Werner, J.M. (Author) Mardon, H.J. (Author) |
| Date: | 1 December 2004 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/56743 |
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