Yu, Y., Ulbrich, M., Li, M.H. et al. (6 more authors) (2009) Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. Proceedings of the National Academy of Sciences of the United States of America, 106 (28). pp. 11558-11563. ISSN 0027-8424
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2009 National Academy of Sciences. This is an author produced version of a paper subsequently published in Proceedings of the National Academy of Sciences of the United States of America. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | autosomal dominant polycystic kidney disease; single-molecule imaging; stoichiometry; transient receptor potential channel; X-ray crystallography |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Clinical Sciences Division North (Sheffield) > Sheffield Kidney Institute |
Depositing User: | Miss Anthea Tucker |
Date Deposited: | 05 Aug 2009 09:54 |
Last Modified: | 08 Feb 2013 16:58 |
Published Version: | http://dx.doi.org/10.1073/pnas.0903684106 |
Status: | Published |
Publisher: | National Academy of Sciences |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.0903684106 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:9053 |