Understanding the molecular basis for differential binding of integrins to collagen and gelatin.
Integrin-mediated cell adhesion plays a central role in cell migration and signaling. Overexpression of integrins is also associated with cancer invasion and metastasis. Although a number of problems in integrin-matrix interactions have been studied in detail, the molecular specificity, which increases integrin adhesion to native collagen but results in poor integrin-gelatin interaction, is not understood. In this report, we study the role of individual amino acids in integrin-collagen and integrin-gelatin interactions using long-term (>100 ns) molecular simulations. The results, which are force-field independent, show that denatured collagen induces helical conformations in integrin amino acids and significantly reduces the poly-proline II content, which stabilizes the integrin-collagen interactions. Our simulations provide a possible explanation of the molecular specificity in integrin binding and suggest new targets for regulating integrin-mediated invasion and metastasis.
Zaman
Muhammad H
MH
D001665:Binding Sites; D003094:Collagen / Q000737:chemistry* / Q000648:ultrastructure; D003198:Computer Simulation; D005780:Gelatin / Q000737:chemistry* / Q000648:ultrastructure; D016023:Integrins / Q000737:chemistry* / Q000648:ultrastructure; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding
D016023:Integrins; D005780:Gelatin; D003094:Collagen