Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1939900 | Biochemical and Biophysical Research Communications | 2006 | 8 Pages |
Gelsolin consists of six related domains (G1–G6) and the C-terminal half (G4–G6) acts as a calcium sensor during the activation of the whole molecule, a process that involves large domain movements. In this study, we used targeted molecular dynamics simulations to elucidate the conformational transitions of G4–G6 at an atomic level. Domains G4 and G6 are initially ruptured, followed by a rotation of G6 by ∼90°, which is the dominant conformational change. During this period, local conformational changes occur at the G4 and G5 calcium-binding sites, facilitating large changes in interdomain distances. Alterations in the binding affinities of the calcium ions in these three domains appear to be related to local conformational changes at their binding sites. Analysis of the relative stabilities of the G4–G6-bound calcium ions suggests that they bind first to G6, then to G4, and finally to G5.