Details

Autor(en) / Beteiligte

• Yu, Yong
• Ulbrich, Maximilian H
• Li, Ming-Hui
• Buraei, Zafir
• Chen, Xing-Zhen
• Ong, Albert C.M
• Tong, Liang
• Isacoff, Ehud Y
• Yang, Jian

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2009-07, Vol.106 (28), p.11558-11563

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2009

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.