Biopolym. Cell. 2008; 24(2):101-104.
Structure and Function of Biopolymers
Insertion intermediate of annexin B12 is prone to aggregation on membrane interfaces
1, 2Ladokhin A. S.
  1. Department of Biochemistry and Molecular Biology
    Kansas University Medical Center
    Kansas City, KS, USA, 66160-7421
  2. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


Annexin B12 (ANX) is known to insert across the lipid bilayer at acidic pH in the absence of Ca2+ 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


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