HINGE-BENDING MOTIONS IN ANNEXINS - MOLECULAR-DYNAMICS AND ESSENTIAL DYNAMICS OF APO-ANNEXIN-V AND OF CALCIUM BOUND ANNEXIN-V AND ANNEXIN-I

Annexins are homologous proteins that bind to membranes in a calcium d ependent manner, but for which precise physiological roles have yet to be defined. Most annexins are composed of a planar array of four homo logous repeats, each containing five alpha-helices and associated into two modules. Annexin V forms a voltage-gated calcium channel in phosp holipid bilayers. It has been proposed that the hydrophilic pore in th e centre of the molecule may represent the ion conduction pathway and that a hinge movement in annexin V causes a variation of the inter-mod ule angle and opens the calcium ion path. Here we present the results of molecular dynamics simulations of apo-annexin V and of calcium-boun d annexin V and annexin I. The three simulations show significant diff erences in conformation and dynamics. The essential dynamics method wa s used to study the essential subspace of annexin V and showed that on e of the essential motions corresponds to the postulated hinge motion. The hinge residues were located between repeats but: belong to helice s rather than to the links between helices. Calcium binding to annexin V led to a limitation of this hinge motion with more open conformatio ns being favoured.