Sponsor
This work was supported by NIH grant R01 GM079233.
Published In
Structure
Document Type
Post-Print
Publication Date
9-2008
Subjects
Nuclear magnetic resonance spectroscopy, Aquaporins, Calmodulin, Phosphorylation, Binding proteins
Abstract
Aquaporins (AQPs) are a family of ubiquitous membrane channels that conduct water across cell membranes. AQPs form homo-tetramers 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 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 non-canonical fashion, suggesting a form of co-operativity 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.
DOI
10.1016/j.str.2008.06.011
Persistent Identifier
http://archives.pdx.edu/ds/psu/21528
Citation Details
Reichow, S. L., & Gonen, T. (2008). Noncanonical binding of calmodulin to aquaporin-0: implications for channel regulation. Structure, 16(9), 1389-1398.
Description
This is the authors' version of an article that subsequently appeared in Structure, 2008 September 10; 16(9): 1389–1398. May be found at https://doi.org/10.1016/j.str.2008.06.011.
Note: At the time of writing, Steve Reichow was affiliated with the University of Washington.