Acidic pH-induced folding of annexin VI is a prerequisite for its insertion into lipid bilayers and formation of ion channels by the protein molecules

Abstract

SPECIFIC AIMSWe tested the hypothesis that annexin VI (AnxVI), a member of a family of Ca2+ and lipid binding proteins, can interact with membranes in a Ca2+-independent manner and behave as a membrane integral protein. For this purpose, we investigated the consequences of AnxVI pH-dependent binding to lipid membranes, such as the formation of ion channels by the annexin molecules and pH-induced conformational changes of AnxVI, to understand some functional aspects of the protein in vivo, particularly under pathological conditions, connected with local fluctuations of pH.PRINCIPAL FINDINGS1. The binding of AnxVI to phospholipids in a Ca2+-insensitive, pH-dependent manner constitutes an alternative to the Ca2+ bridging mechanism of interaction of annexins with membranesThe Ca2+-independent binding of AnxVI to asolectin liposomes is stimulated by acidic pH; half-maximal binding occurred at pH 5.3. The lipid composition of liposomes is not crucial for AnxVI–lipid interactions at low pH. The binding at lower ...