This application is aimed at characterizing some of structural-functional features of Annexin XII from the Hydra vulgaris. Based on previous results, the investigator proposes new models for annexin-mediated membrane aggregation/fusion and channel activity. Studies will also examine the mechanism of interaction between annexin XII and lipid bilayers. The investigator notes that elucidation of the structure of membrane-bound annexin will provide a solid foundation for evaluating their proposed biological functions.
Four Specific Aims will be pursued: (1) to determine the structure of annexin XII bound to phospholipid bilayers; (2) to investigate the molecular mechanisms of annexin-induced ion flux across bilayers; (3) to determine whether the annexin XII hexamers mediate vesicle aggregation/fusion; and (4) to determine the structural/ functional consequence of annexin XII phosphorylation

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Cellular Biology and Physiology Subcommittee 1 (CBY)
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University of California Irvine
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Fischer, Torsten; Lu, Lucy; Haigler, Harry T et al. (2007) Annexin B12 is a sensor of membrane curvature and undergoes major curvature-dependent structural changes. J Biol Chem 282:9996-10004
Hegde, Balachandra G; Isas, J Mario; Zampighi, Guido et al. (2006) A novel calcium-independent peripheral membrane-bound form of annexin B12. Biochemistry 45:934-42
Patel, Darshana R; Isas, J Mario; Ladokhin, Alexey S et al. (2005) The conserved core domains of annexins A1, A2, A5, and B12 can be divided into two groups with different Ca2+-dependent membrane-binding properties. Biochemistry 44:2833-44
Kim, Yujin E; Isas, Jose Mario; Haigler, Harry T et al. (2005) A helical hairpin region of soluble annexin B12 refolds and forms a continuous transmembrane helix at mildly acidic pH. J Biol Chem 280:32398-404
Isas, Jose Mario; Kim, Yujin E; Jao, Christine C et al. (2005) Calcium- and membrane-induced changes in the structure and dynamics of three helical hairpins in annexin B12. Biochemistry 44:16435-44
Ladokhin, Alexey S; Haigler, Harry T (2005) Reversible transition between the surface trimer and membrane-inserted monomer of annexin 12. Biochemistry 44:3402-9
Isas, J Mario; Langen, Ralf; Hubbell, Wayne L et al. (2004) Structure and dynamics of a helical hairpin that mediates calcium-dependent membrane binding of annexin B12. J Biol Chem 279:32492-8
Peng, S; Publicover, N G; Airey, J A et al. (2004) Diffusion of single cardiac ryanodine receptors in lipid bilayers is decreased by annexin 12. Biophys J 86:145-51
Risse, T; Hubbell, W L; Isas, J M et al. (2003) Structure and dynamics of annexin 12 bound to a planar lipid bilayer. Phys Rev Lett 91:188101
Isas, J Mario; Patel, Darshana R; Jao, Christine et al. (2003) Global structural changes in annexin 12. The roles of phospholipid, Ca2+, and pH. J Biol Chem 278:30227-34

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