AVS 46th International Symposium
    Biomaterial Interfaces Group Friday Sessions
       Session BI-FrM

Paper BI-FrM4
The Fibronectin Type III Domain: A Scaffold for a Molecular Recognition Switch

Friday, October 29, 1999, 9:20 am, Room 613/614

Session: Interface, Properties, and Modification
Presenter: A. Krammer, University of Washington
Authors: A. Krammer, University of Washington
H. Lu, University of Illinois, Urbana-Champaign
B. Isralewitz, University of Illinois, Urbana-Champaign
K. Schulten, University of Illinois, Urbana-Champaign
V. Vogel, University of Washington
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The forced unfolding of fibronectin's tenth type III module (FnIII10) was simulated by steered molecular dynamics (SMD) indicating that mechanical tension applied to the module's termini renders its RGD loop inaccessible to cell surface integrins. FnIII10 possesses a beta-sandwich motif consisting of seven beta-strands (A-G) that are arranged in two antiparallel sheets with the RGD peptide sequence located at the apex of the FG loop. Computer simulations now reveal that the b-strand G separates from the module at an early stage of unfolding while the remaining fold experiences only small structural perturbations. Consequently, the RGD peptide is pulled closer to the module's surface as the FG loop unravels. A molecular scale picture of the forced unfolding pathway will be discussed as well as its implications for the understanding of cell-surface interactions.