Hinge-bending motions in annexins: molecular dynamics and essential dynamics of apo-annexin V and of calcium bound annexin V and I

Annexins are homologous proteins that bind to membranes in a calciumdependent manner, but for which precise physiological roles have yet to bedefined. Most annexins are composed of a planar array of four homologousrepeats, each containing five alpha-helices and associated into twomodules. Annexin V forms a voltage-gated calcium channel in phospholipidbilayers. It has been proposed that the hydrophilic pore in the centre ofthe molecule may represent the ion conduction pathway and that a hingemovement in annexin V causes a variation of the inter- module angle andopens the calcium ion path. Here we present the results of moleculardynamics simulations of apo-annexin V and of calcium-bound annexin V andannexin I. The three simulations show significant differences inconformation and dynamics. The essential dynamics method was used to studythe essential subspace of annexin V and showed that one of the essentialmotions corresponds to the postulated hinge motion. The hinge residues werelocated between repeats but belong to helices rather than to the linksbetween helices. Calcium binding to annexin V led to a limitation of thishinge motion with more open conformations being favoured.