{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:29:53Z","timestamp":1781850593951,"version":"3.54.5"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,6,21]]},"abstract":"<jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in TRPP2 and PKD1, which form an ion channel\/receptor complex containing three TRPP2 and one PKD1. A TRPP2 C-terminal coiled-coil trimer, critical for the assembly of this complex, associates with a single PKD1 C-terminal coiled-coil. Many ADPKD pathogenic mutations result in the abolishment of the TRPP2\/PKD1 coiled-coil complex. To gain molecular and functional insights into this heterotetrameric complex, we computationally constructed a structural model by using a two-step docking strategy, based on a known crystal structure of the TRPP2 coiled-coil trimer. The model shows that this tetrameric complex has a novel di-trimer configuration: An upstream trimer made of three TRPP2 helices and a downstream trimer made of two TRPP2 helices and one PKD1 helix. Mutagenesis and biochemical analysis identified critical TRPP2\/PKD1 interface contacts essential for the heteromeric coiled-coil complex. Mutation of these interface positions in the full-length proteins showed that these interactions were critical for the assembly of the full-length complex in cells. Our results provide a means to specifically weaken the TRPP2 and PKD1 association, thus facilitating future in vitro and in vivo studies on the functional importance of this association.<\/jats:p>","DOI":"10.1073\/pnas.1017669108","type":"journal-article","created":{"date-parts":[[2011,6,4]],"date-time":"2011-06-04T00:31:55Z","timestamp":1307147515000},"page":"10133-10138","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":56,"title":["Structural model of the TRPP2\/PKD1 C-terminal coiled-coil complex produced by a combined computational and experimental approach"],"prefix":"10.1073","volume":"108","author":[{"given":"Jiang","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute and Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 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