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XB-ART-40448
Proc Natl Acad Sci U S A. July 14, 2009; 106 (28): 11558-63.

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

Yu Y , Ulbrich MH , Li MH , Buraei Z , Chen XZ , Ong AC , Tong L , Isacoff EY , Yang J .


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.

PubMed ID: 19556541
PMC ID: PMC2710685
Article link: Proc Natl Acad Sci U S A.
Grant support: GM085234 NIGMS NIH HHS , GR071201 Wellcome Trust , NS035549 NINDS NIH HHS , NS045383 NINDS NIH HHS , R01 NS035549-13 NINDS NIH HHS

Genes referenced: pkd1
Antibodies referenced:

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