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Structure. 2008 Sep 10;16(9):1389-98. doi: 10.1016/j.str.2008.06.011.

Noncanonical binding of calmodulin to aquaporin-0: implications for channel regulation.

Author information

1
Department of Biochemistry, University of Washington, Box 357350, Seattle, WA 98195-7350, USA.

Abstract

Aquaporins (AQPs) are a family of ubiquitous membrane channels that conduct water across cell membranes. AQPs form homotetramers containing four functional and independent water pores. Aquaporin-0 (AQP0) is expressed in the eye lens, where its water permeability is regulated by calmodulin (CaM). Here we use a combination of biochemical methods and NMR spectroscopy to probe the interaction between AQP0 and CaM. We show that CaM binds the AQP0 C-terminal domain in a calcium-dependent manner. We demonstrate that only two CaM molecules bind a single AQP0 tetramer in a noncanonical fashion, suggesting a form of cooperativity between AQP0 monomers. Based on these results, we derive a structural model of the AQP0/CaM complex, which suggests CaM may be inhibitory to channel permeability by capping the vestibules of two monomers within the AQP0 tetramer. Finally, phosphorylation within AQP0's CaM binding domain inhibits the AQP0/CaM interaction, suggesting a temporal regulatory mechanism for complex formation.

PMID:
18786401
PMCID:
PMC2605016
DOI:
10.1016/j.str.2008.06.011
[Indexed for MEDLINE]
Free PMC Article

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