Name
Title | ||
|---|---|---|
High Affinity vs. Native Fibronectin in the Modulation of alpha v beta 3 Integrin Conformational Dynamics: Insights from Computational Analyses and Implications for Molecular Design |
Abstract | ||
|---|---|---|
Understanding how binding events modulate functional motions of multidomain proteins is a major issue in chemical biology. We address several aspects of this problem by analyzing the differential dynamics of alpha v beta 3 integrin bound to wild type (wtFN10, agonist) or high affinity (hFN10, antagonist) mutants of fibronectin. We compare the dynamics of complexes from large-scale domain motions to inter-residue coordinated fluctuations to characterize the distinctive traits of conformational evolution and shed light on the determinants of differential alpha v beta 3 activation induced by different FN sequences. We propose an allosteric model for ligand-based integrin modulation: the conserved integrin binding pocket anchors the ligand, while different residues on the two FN10's act as the drivers that reorganize relevant interaction networks, guiding the shift towards inactive (hFN10-bound) or active states (wtFN10-bound). We discuss the implications of results for the design of integrin inhibitors. |
Year | DOI | Venue |
|---|---|---|
2017 | 10.1371/journal.pcbi.1005334 | PLOS COMPUTATIONAL BIOLOGY |
Field | DocType | Volume |
Biology,Cell biology,Integrin,Bioinformatics,Fibronectin | Journal | 13 |
Issue | ISSN | Citations |
1 | 1553-7358 | 0 |
PageRank | References | Authors |
0.34 | 6 | 4 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Antonella Paladino | 1 | 0 | 0.34 |
| Monica Civera | 2 | 0 | 0.68 |
| L Belvisi | 3 | 6 | 2.65 |
| Giorgio Colombo | 4 | 49 | 11.77 |