Unraveling the Role of Protein-Proteins Interactions of Annexin at the Membrane

Abstract

Protein-membrane interactions are a vital mechanism of propagating signals both across the membrane and between cells. One method of signal propagation is the formation of lipid microdomains that allow the preferential clustering of specific lipid types and proteins. To address this type of signal propagation, we investigated how lipid microdomains form in response to annexin binding to model membranes. Annexins bind to negatively charged (e.g., phosphatidylserine [PS]) membranes in a calcium-dependent manner and lead to the formation of PS-enriched microdomains in supported planar bilayers. Two distinct mechanisms of signal propagation via protein-lipid binding are addressed. First, we hypothesize that proteins can transmit binding information via the ordering of the lipid acyl chains upon binding. Alternatively, we predict that when a protein binds a specific lipid preferentially, protein-protein interactions are enhanced on a membrane surface. The role of lipid acyl chain ordering and protein-protein interactions as distinct mechanisms of signal propagation through lipid binding will be illustrated.