Biopolymers and cell. 2008; 24 (2): 100 - 104

Insertion intermediate of annexin B12 is prone to aggregation on membrane interfaces

A. S. Ladokhin

Annexin B12 (ANX) is known to insert across the lipid bilayer at acidic pH in the absence of Ca+2 and to form a pore-like structure consisting of several transmembrane helices, most of which are unknown. Our previous studies demonstrate that the insertion proceeds via an interfacial refolded intermediate state, which can be stabilized by anionic lipids. Energy transfer measurements in a mixture of donor- and acceptor-labeled ANX indicate that this interfacial intermediate, unlike the final transmembrane conformation, is prone to aggregation. Such aggregation of a non-inserted ANX may have implications for a possible general mechanism of misfolding of membrane proteins.

Keywords:membrane protein, transmembrane helix, folding/insertion intermediate, lipid bilayer topology, circular dichroism, FRET.