Novel Organization and Properties of Annexin 2-Membrane Complexes

Olivier Lambert, Nükhet Cavusoglu, Jacques Gallay, Michel Vincent, Jean Louis Rigaud, Jean-Pierre Henry, Jesus Ayala-Sanmartin
2003 Journal of Biological Chemistry  
Annexin 2 belongs to the annexin family of proteins that bind to phospholipid membranes in a Ca 2؉ -dependent manner. Here we show that, under mild acidic conditions, annexin 2 binds to and aggregates membranes containing anionic phospholipids, a fact that questions the mechanism of its interaction with membranes via Ca 2؉ bridges only. The H ؉ sensitivity of annexin 2-mediated aggregation is modulated by lipid composition (i.e. cholesterol content). Cryo-electron microscopy of aggregated
more » ... mes revealed that both the monomeric and the tetrameric forms of the protein form bridges between the liposomes at acidic pH. Monomeric annexin 2 induced two different organizations of the membrane junctions. The first resembled that obtained at pH 7 in the presence of Ca 2؉ . For the tetramer, the arrangement was different. These bridges seemed more flexible than the Ca 2؉ -mediated junctions allowing the invagination of membranes. Time-resolved fluorescence analysis at mild acidic pH and the measurement of Stokes radius revealed that the protein undergoes conformational changes similar to those induced by Ca 2؉ . Labeling with the lipophilic probe 3-(trifluoromethyl)-3-(m-[ 125 I]iodophenyl)diazirine indicated that the protein has access to the hydrophobic part of the membrane at both acidic pH in the absence of Ca 2؉ and at neutral pH in the presence of Ca 2؉ . Models for the membrane interactions of annexin 2 at neutral pH in the presence of Ca 2؉ and at acidic pH are discussed.
doi:10.1074/jbc.m313657200 pmid:14701819 fatcat:dxy2tn4axjh7ve3mfwz22ohtqq