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Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11558-63. doi: 10.1073/pnas.0903684106. Epub 2009 Jun 25.

Structural and molecular basis of the assembly of the TRPP2/PKD1 complex.

Author information

1
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

Abstract

Mutations in PKD1 and TRPP2 account for nearly all cases of autosomal dominant polycystic kidney disease (ADPKD). These 2 proteins form a receptor/ion channel complex on the cell surface. Using a combination of biochemistry, crystallography, and a single-molecule method to determine the subunit composition of proteins in the plasma membrane of live cells, we find that this complex contains 3 TRPP2 and 1 PKD1. A newly identified coiled-coil domain in the C terminus of TRPP2 is critical for the formation of this complex. This coiled-coil domain forms a homotrimer, in both solution and crystal structure, and binds to a single coiled-coil domain in the C terminus of PKD1. Mutations that disrupt the TRPP2 coiled-coil domain trimer abolish the assembly of both the full-length TRPP2 trimer and the TRPP2/PKD1 complex and diminish the surface expression of both proteins. These results have significant implications for the assembly, regulation, and function of the TRPP2/PKD1 complex and the pathogenic mechanism of some ADPKD-producing mutations.

PMID:
19556541
PMCID:
PMC2710685
DOI:
10.1073/pnas.0903684106
[Indexed for MEDLINE]
Free PMC Article

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