title: Phosphorylation primes vinculin for activation.
abstract: Vinculin phosphorylation has been implicated as a potential mechanism for focal adhesion growth and maturation. Four vinculin residues-Y100, S1033, S1045, and Y1065-are phosphorylated by kinases during focal adhesion maturation. In this study, phosphorylation at each of these residues is simulated using molecular dynamics models. The simulations demonstrate that once each phosphorylated vinculin structure is at equilibrium, significant local conformational changes result that may impact either vinculin activation or vinculin binding to actin and PIP2. Simulation of vinculin activation after phosphorylation shows that the added phosphoryl groups can prime vinculin for activation. It remains to be seen if vinculin can be phosphorylated at S1033 in vivo, but these simulations highlight that in the event of a S1033 phophorylation vinculin will likely be primed for activation.
authors: Molecular Cell Biomechanics Laboratory, Department of Bioengineering, University of California, Berkeley, CA, USA.
authors: Javad
authors: J
authors: Golji
authors: Timothy
authors: T
authors: Wendorff
authors: Mohammad R K
authors: MR
authors: Mofrad
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000648:ultrastructure*; D017434:Protein Structure, Tertiary; D016596:Vinculin / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D016596:Vinculin; D011494:Protein Kinases