{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:49:18Z","timestamp":1792172958441,"version":"4.4.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T00:00:00Z","timestamp":1482105600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2017,2]]},"DOI":"10.1038\/nsmb.3343","type":"journal-article","created":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T16:00:01Z","timestamp":1482163201000},"page":"114-122","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":190,"title":["Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2)"],"prefix":"10.1038","volume":"24","author":[{"given":"Mariana","family":"Grieben","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9661-2607","authenticated-orcid":false,"given":"Ashley C W","family":"Pike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitra A","family":"Shintre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Venturi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"El-Ajouz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Tessitore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leela","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhashish","family":"Mukhopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pravin","family":"Mahajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rod","family":"Chalk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola A","family":"Burgess-Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sitsapesan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0348-7323","authenticated-orcid":false,"given":"Juha T","family":"Huiskonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9138-2937","authenticated-orcid":false,"given":"Elisabeth P","family":"Carpenter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,19]]},"reference":[{"key":"BFnsmb3343_CR1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1056\/NEJMra022161","volume":"350","author":"PD Wilson","year":"2004","unstructured":"Wilson, P.D. Polycystic kidney disease. N. Engl. J. Med. 350, 151\u2013164 (2004).","journal-title":"N. Engl. J. Med."},{"key":"BFnsmb3343_CR2","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/S0140-6736(98)03495-3","volume":"353","author":"N Hateboer","year":"1999","unstructured":"Hateboer, N. et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2: European PKD1-PKD2 Study Group. Lancet 353, 103\u2013107 (1999).","journal-title":"Lancet"},{"key":"BFnsmb3343_CR3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/aps.2015.126","volume":"37","author":"J Du","year":"2016","unstructured":"Du, J., Fu, J., Xia, X.M. & Shen, B. The functions of TRPP2 in the vascular system. Acta Pharmacol. Sin. 37, 13\u201318 (2016).","journal-title":"Acta Pharmacol. Sin."},{"key":"BFnsmb3343_CR4","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1053\/j.ackd.2010.01.001","volume":"17","author":"AB Chapman","year":"2010","unstructured":"Chapman, A.B., Stepniakowski, K. & Rahbari-Oskoui, F. Hypertension in autosomal dominant polycystic kidney disease. Adv. Chronic Kidney Dis. 17, 153\u2013163 (2010).","journal-title":"Adv. Chronic Kidney Dis."},{"key":"BFnsmb3343_CR5","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1681\/ASN.2011010084","volume":"22","author":"A Karihaloo","year":"2011","unstructured":"Karihaloo, A. et al. Macrophages promote cyst growth in polycystic kidney disease. J. Am. Soc. Nephrol. 22, 1809\u20131814 (2011).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFnsmb3343_CR6","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1126\/science.272.5266.1339","volume":"272","author":"T Mochizuki","year":"1996","unstructured":"Mochizuki, T. et al. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272, 1339\u20131342 (1996).","journal-title":"Science"},{"key":"BFnsmb3343_CR7","doi-asserted-by":"crossref","unstructured":"The International Polycystic Kidney Disease Consortium. Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. Cell 81, 289\u2013298 (1995).","DOI":"10.1016\/0092-8674(95)90339-9"},{"key":"BFnsmb3343_CR8","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/S0960-9822(02)00869-2","volume":"12","author":"P Pennekamp","year":"2002","unstructured":"Pennekamp, P. et al. The ion channel polycystin-2 is required for left-right axis determination in mice. Curr. Biol. 12, 938\u2013943 (2002).","journal-title":"Curr. Biol."},{"key":"BFnsmb3343_CR9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/S0092-8674(03)00511-7","volume":"114","author":"J McGrath","year":"2003","unstructured":"McGrath, J., Somlo, S., Makova, S., Tian, X. & Brueckner, M. Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114, 61\u201373 (2003).","journal-title":"Cell"},{"key":"BFnsmb3343_CR10","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1053\/j.ajkd.2011.05.015","volume":"58","author":"S Bataille","year":"2011","unstructured":"Bataille, S. et al. Association of PKD2 (polycystin 2) mutations with left-right laterality defects. Am. J. Kidney Dis. 58, 456\u2013460 (2011).","journal-title":"Am. J. Kidney Dis."},{"key":"BFnsmb3343_CR11","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1097\/01.ASN.0000029587.47950.25","volume":"13","author":"BK Yoder","year":"2002","unstructured":"Yoder, B.K., Hou, X. & Guay-Woodford, L.M. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J. Am. Soc. Nephrol. 13, 2508\u20132516 (2002).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFnsmb3343_CR12","doi-asserted-by":"publisher","first-page":"R378","DOI":"10.1016\/S0960-9822(02)00877-1","volume":"12","author":"GJ Pazour","year":"2002","unstructured":"Pazour, G.J., San Agustin, J.T., Follit, J.A., Rosenbaum, J.L. & Witman, G.B. Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease. Curr. Biol. 12, R378\u2013R380 (2002).","journal-title":"Curr. Biol."},{"key":"BFnsmb3343_CR13","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/ng1076","volume":"33","author":"SM Nauli","year":"2003","unstructured":"Nauli, S.M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129\u2013137 (2003).","journal-title":"Nat. Genet."},{"key":"BFnsmb3343_CR14","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s00232-001-0075-4","volume":"184","author":"HA Praetorius","year":"2001","unstructured":"Praetorius, H.A. & Spring, K.R. Bending the MDCK cell primary cilium increases intracellular calcium. J. Membr. Biol. 184, 71\u201379 (2001).","journal-title":"J. Membr. Biol."},{"key":"BFnsmb3343_CR15","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/nature17426","volume":"531","author":"M Delling","year":"2016","unstructured":"Delling, M. et al. Primary cilia are not calcium-responsive mechanosensors. Nature 531, 656\u2013660 (2016).","journal-title":"Nature"},{"key":"BFnsmb3343_CR16","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/nature17313","volume":"531","author":"DP Norris","year":"2016","unstructured":"Norris, D.P. & Jackson, P.K. Cell biology: calcium contradictions in cilia. Nature 531, 582\u2013583 (2016).","journal-title":"Nature"},{"key":"BFnsmb3343_CR17","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/ncb754","volume":"4","author":"P Koulen","year":"2002","unstructured":"Koulen, P. et al. Polycystin-2 is an intracellular calcium release channel. Nat. Cell Biol. 4, 191\u2013197 (2002).","journal-title":"Nat. Cell Biol."},{"key":"BFnsmb3343_CR18","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/sj.embor.7400745","volume":"7","author":"A Giamarchi","year":"2006","unstructured":"Giamarchi, A. et al. The versatile nature of the calcium-permeable cation channel TRPP2. EMBO Rep. 7, 787\u2013793 (2006).","journal-title":"EMBO Rep."},{"key":"BFnsmb3343_CR19","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1146\/annurev.physiol.68.040204.100431","volume":"68","author":"IS Ramsey","year":"2006","unstructured":"Ramsey, I.S., Delling, M. & Clapham, D.E. An introduction to TRP channels. Annu. Rev. Physiol. 68, 619\u2013647 (2006).","journal-title":"Annu. Rev. Physiol."},{"key":"BFnsmb3343_CR20","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1073\/pnas.98.3.1182","volume":"98","author":"S Gonz\u00e1lez-Perrett","year":"2001","unstructured":"Gonz\u00e1lez-Perrett, S. et al. Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel. Proc. Natl. Acad. Sci. USA 98, 1182\u20131187 (2001).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnsmb3343_CR21","doi-asserted-by":"publisher","first-page":"24959","DOI":"10.1074\/jbc.M105084200","volume":"277","author":"S Gonzalez-Perrett","year":"2002","unstructured":"Gonzalez-Perrett, S. et al. Voltage dependence and pH regulation of human polycystin-2-mediated cation channel activity. J. Biol. Chem. 277, 24959\u201324966 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb3343_CR22","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/ki.2009.128","volume":"76","author":"VE Torres","year":"2009","unstructured":"Torres, V.E. & Harris, P.C. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int. 76, 149\u2013168 (2009).","journal-title":"Kidney Int."},{"key":"BFnsmb3343_CR23","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1038\/35050128","volume":"408","author":"K Hanaoka","year":"2000","unstructured":"Hanaoka, K. et al. Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature 408, 990\u2013994 (2000).","journal-title":"Nature"},{"key":"BFnsmb3343_CR24","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0092-8674(00)81570-6","volume":"93","author":"G Wu","year":"1998","unstructured":"Wu, G. et al. Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell 93, 177\u2013188 (1998).","journal-title":"Cell"},{"key":"BFnsmb3343_CR25","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/ng0792-235","volume":"1","author":"ST Reeders","year":"1992","unstructured":"Reeders, S.T. Multilocus polycystic disease. Nat. Genet. 1, 235\u2013237 (1992).","journal-title":"Nat. Genet."},{"key":"BFnsmb3343_CR26","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S1471-4914(01)01953-0","volume":"7","author":"Y Pei","year":"2001","unstructured":"Pei, Y. A \u201ctwo-hit\u201d model of cystogenesis in autosomal dominant polycystic kidney disease? Trends Mol. Med. 7, 151\u2013156 (2001).","journal-title":"Trends Mol. Med."},{"key":"BFnsmb3343_CR27","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1093\/hmg\/ddp024","volume":"18","author":"P Zhang","year":"2009","unstructured":"Zhang, P. et al. The multimeric structure of polycystin-2 (TRPP2): structural-functional correlates of homo- and hetero-multimers with TRPC1. Hum. Mol. Genet. 18, 1238\u20131251 (2009).","journal-title":"Hum. Mol. Genet."},{"key":"BFnsmb3343_CR28","doi-asserted-by":"publisher","first-page":"E2363","DOI":"10.1073\/pnas.1517066113","volume":"113","author":"M Arif Pavel","year":"2016","unstructured":"Arif Pavel, M. et al. Function and regulation of TRPP2 ion channel revealed by a gain-of-function mutant. Proc. Natl. Acad. Sci. USA 113, E2363\u2013E2372 (2016).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnsmb3343_CR29","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.neuron.2010.08.021","volume":"67","author":"WA Catterall","year":"2010","unstructured":"Catterall, W.A. Ion channel voltage sensors: structure, function, and pathophysiology. Neuron 67, 915\u2013928 (2010).","journal-title":"Neuron"},{"key":"BFnsmb3343_CR30","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/nature12822","volume":"504","author":"M Liao","year":"2013","unstructured":"Liao, M., Cao, E., Julius, D. & Cheng, Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504, 107\u2013112 (2013).","journal-title":"Nature"},{"key":"BFnsmb3343_CR31","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/nsmb.3159","volume":"23","author":"L Zubcevic","year":"2016","unstructured":"Zubcevic, L. et al. Cryo-electron microscopy structure of the TRPV2 ion channel. Nat. Struct. Mol. Biol. 23, 180\u2013186 (2016).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFnsmb3343_CR32","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.cell.2016.09.048","volume":"167","author":"PS Shen","year":"2016","unstructured":"Shen, P.S. et al. The structure of the polycystic kidney disease channel pkd2 in lipid nanodiscs. Cell 167, 763\u2013773 e11 (2016).","journal-title":"Cell"},{"key":"BFnsmb3343_CR33","doi-asserted-by":"publisher","first-page":"25967","DOI":"10.1074\/jbc.273.40.25967","volume":"273","author":"H Nomura","year":"1998","unstructured":"Nomura, H. et al. Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects. J. Biol. Chem. 273, 25967\u201325973 (1998).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb3343_CR34","doi-asserted-by":"publisher","first-page":"14854","DOI":"10.1074\/jbc.M114.562264","volume":"289","author":"A Hofherr","year":"2014","unstructured":"Hofherr, A., Wagner, C., Fedeles, S., Somlo, S. & K\u00f6ttgen, M. N-glycosylation determines the abundance of the transient receptor potential channel TRPP2. J. Biol. Chem. 289, 14854\u201314867 (2014).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb3343_CR35","doi-asserted-by":"publisher","unstructured":"Wilkes, M. et al. Molecular insights into lipid-assisted Ca2+ regulation of the TRP channel Polycystin-2. Nat. Struct. Mol. Biol. \n                    http:\/\/dx.doi.org\/10.1038\/nsmb.3357\n                    \n                   (in the press).","DOI":"10.1038\/nsmb.3357"},{"key":"BFnsmb3343_CR36","doi-asserted-by":"publisher","first-page":"W529","DOI":"10.1093\/nar\/gkq399","volume":"38","author":"H Ashkenazy","year":"2010","unstructured":"Ashkenazy, H., Erez, E., Martz, E., Pupko, T. & Ben-Tal, N. ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res. 38, W529\u2013W533 (2010).","journal-title":"Nucleic Acids Res."},{"key":"BFnsmb3343_CR37","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/nature14367","volume":"520","author":"CE Paulsen","year":"2015","unstructured":"Paulsen, C.E., Armache, J.P., Gao, Y., Cheng, Y. & Julius, D. Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 520, 511\u2013517 (2015).","journal-title":"Nature"},{"key":"BFnsmb3343_CR38","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/S0263-7855(97)00009-X","volume":"14","author":"OS Smart","year":"1996","unstructured":"Smart, O.S., Neduvelil, J.G., Wang, X., Wallace, B.A. & Sansom, M.S. HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J. Mol. Graph. 14, 354\u2013360, 376 (1996).","journal-title":"J. Mol. Graph."},{"key":"BFnsmb3343_CR39","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature12775","volume":"505","author":"L Tang","year":"2014","unstructured":"Tang, L. et al. Structural basis for Ca2+ selectivity of a voltage-gated calcium channel. Nature 505, 56\u201361 (2014).","journal-title":"Nature"},{"key":"BFnsmb3343_CR40","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/nature17975","volume":"534","author":"K Saotome","year":"2016","unstructured":"Saotome, K., Singh, A.K., Yelshanskaya, M.V. & Sobolevsky, A.I. Crystal structure of the epithelial calcium channel TRPV6. Nature 534, 506\u2013511 (2016).","journal-title":"Nature"},{"key":"BFnsmb3343_CR41","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1242\/jcs.02818","volume":"119","author":"L Geng","year":"2006","unstructured":"Geng, L. et al. Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif. J. Cell Sci. 119, 1383\u20131395 (2006).","journal-title":"J. Cell Sci."},{"key":"BFnsmb3343_CR42","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1096\/fj.13-247106","volume":"28","author":"IY Kuo","year":"2014","unstructured":"Kuo, I.Y. et al. The number and location of EF hand motifs dictates the calcium dependence of polycystin-2 function. FASEB J. 28, 2332\u20132346 (2014).","journal-title":"FASEB J."},{"key":"BFnsmb3343_CR43","doi-asserted-by":"publisher","first-page":"4141","DOI":"10.1113\/JP270933","volume":"594","author":"Y Yang","year":"2016","unstructured":"Yang, Y. & Ehrlich, B.E. Structural studies of the C-terminal tail of polycystin-2 (PC2) reveal insights into the mechanisms used for the functional regulation of PC2. J. Physiol. (Lond.) 594, 4141\u20134149 (2016).","journal-title":"J. Physiol. (Lond.)"},{"key":"BFnsmb3343_CR44","doi-asserted-by":"publisher","first-page":"4675","DOI":"10.1111\/j.1742-4658.2008.06616.x","volume":"275","author":"XZ Chen","year":"2008","unstructured":"Chen, X.Z. et al. Submembraneous microtubule cytoskeleton: interaction of TRPP2 with the cell cytoskeleton. FEBS J. 275, 4675\u20134683 (2008).","journal-title":"FEBS J."},{"key":"BFnsmb3343_CR45","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1093\/hmg\/ddl070","volume":"15","author":"AJ Streets","year":"2006","unstructured":"Streets, A.J., Moon, D.J., Kane, M.E., Obara, T. & Ong, A.C. Identification of an N-terminal glycogen synthase kinase 3 phosphorylation site which regulates the functional localization of polycystin-2 in vivo and in vitro. Hum. Mol. Genet. 15, 1465\u20131473 (2006).","journal-title":"Hum. Mol. Genet."},{"key":"BFnsmb3343_CR46","doi-asserted-by":"publisher","first-page":"3853","DOI":"10.1091\/mbc.e10-04-0377","volume":"21","author":"AJ Streets","year":"2010","unstructured":"Streets, A.J., Needham, A.J., Gill, S.K. & Ong, A.C. Protein kinase D-mediated phosphorylation of polycystin-2 (TRPP2) is essential for its effects on cell growth and calcium channel activity. Mol. Biol. Cell 21, 3853\u20133865 (2010).","journal-title":"Mol. Biol. Cell"},{"key":"BFnsmb3343_CR47","doi-asserted-by":"publisher","first-page":"19987","DOI":"10.1074\/jbc.M312031200","volume":"279","author":"Y Cai","year":"2004","unstructured":"Cai, Y. et al. Calcium dependence of polycystin-2 channel activity is modulated by phosphorylation at Ser812. J. Biol. Chem. 279, 19987\u201319995 (2004).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb3343_CR48","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/nar\/29.1.308","volume":"29","author":"ST Sherry","year":"2001","unstructured":"Sherry, S.T. et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 29, 308\u2013311 (2001).","journal-title":"Nucleic Acids Res."},{"key":"BFnsmb3343_CR49","doi-asserted-by":"publisher","first-page":"5129","DOI":"10.1172\/JCI67273","volume":"124","author":"Y Cai","year":"2014","unstructured":"Cai, Y. et al. Altered trafficking and stability of polycystins underlie polycystic kidney disease. J. Clin. Invest. 124, 5129\u20135144 (2014).","journal-title":"J. Clin. Invest."},{"key":"BFnsmb3343_CR50","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1126\/science.1261512","volume":"347","author":"YY Dong","year":"2015","unstructured":"Dong, Y.Y. et al. K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science 347, 1256\u20131259 (2015).","journal-title":"Science"},{"key":"BFnsmb3343_CR51","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.cell.2016.02.002","volume":"164","author":"M Schewe","year":"2016","unstructured":"Schewe, M. et al. A non-canonical voltage-sensing mechanism controls gating in K2P K+ channels. Cell 164, 937\u2013949 (2016).","journal-title":"Cell"},{"key":"BFnsmb3343_CR52","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/nature12823","volume":"504","author":"E Cao","year":"2013","unstructured":"Cao, E., Liao, M., Cheng, Y. & Julius, D. TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504, 113\u2013118 (2013).","journal-title":"Nature"},{"key":"BFnsmb3343_CR53","doi-asserted-by":"publisher","first-page":"7214","DOI":"10.1074\/jbc.M805890200","volume":"284","author":"EY Park","year":"2009","unstructured":"Park, E.Y. et al. Cyst formation in kidney via B-Raf signaling in the PKD2 transgenic mice. J. Biol. Chem. 284, 7214\u20137222 (2009).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb3343_CR54","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/nmeth.2472","volume":"10","author":"X Li","year":"2013","unstructured":"Li, X. et al. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat. Methods 10, 584\u2013590 (2013).","journal-title":"Nat. Methods"},{"key":"BFnsmb3343_CR55","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/S1047-8477(03)00069-8","volume":"142","author":"JA Mindell","year":"2003","unstructured":"Mindell, J.A. & Grigorieff, N. Accurate determination of local defocus and specimen tilt in electron microscopy. J. Struct. Biol. 142, 334\u2013347 (2003).","journal-title":"J. Struct. Biol."},{"key":"BFnsmb3343_CR56","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jsb.2014.11.010","volume":"189","author":"SH Scheres","year":"2015","unstructured":"Scheres, S.H. Semi-automated selection of cryo-EM particles in RELION-1.3. J. Struct. Biol. 189, 114\u2013122 (2015).","journal-title":"J. Struct. Biol."},{"key":"BFnsmb3343_CR57","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jsb.2006.06.006","volume":"157","author":"JB Heymann","year":"2007","unstructured":"Heymann, J.B. & Belnap, D.M. Bsoft: image processing and molecular modeling for electron microscopy. J. Struct. Biol. 157, 3\u201318 (2007).","journal-title":"J. Struct. Biol."},{"key":"BFnsmb3343_CR58","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.jmb.2003.07.013","volume":"333","author":"PB Rosenthal","year":"2003","unstructured":"Rosenthal, P.B. & Henderson, R. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333, 721\u2013745 (2003).","journal-title":"J. Mol. Biol."},{"key":"BFnsmb3343_CR59","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ultramic.2013.06.004","volume":"135","author":"S Chen","year":"2013","unstructured":"Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24\u201335 (2013).","journal-title":"Ultramicroscopy"},{"key":"BFnsmb3343_CR60","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/nmeth.2727","volume":"11","author":"A Kucukelbir","year":"2014","unstructured":"Kucukelbir, A., Sigworth, F.J. & Tagare, H.D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11, 63\u201365 (2014).","journal-title":"Nat. Methods"},{"key":"BFnsmb3343_CR61","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W.G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"BFnsmb3343_CR62","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nmeth.3286","volume":"12","author":"F DiMaio","year":"2015","unstructured":"DiMaio, F. et al. Atomic-accuracy models from 4.5-\u00c5 cryo-electron microscopy data with density-guided iterative local refinement. Nat. Methods 12, 361\u2013365 (2015).","journal-title":"Nat. Methods"},{"key":"BFnsmb3343_CR63","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1107\/S1399004714021683","volume":"71","author":"A Brown","year":"2015","unstructured":"Brown, A. et al. Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions. Acta Crystallogr. D Biol. Crystallogr. 71, 136\u2013153 (2015).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"BFnsmb3343_CR64","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1107\/S090744491105606X","volume":"68","author":"RA Nicholls","year":"2012","unstructured":"Nicholls, R.A., Long, F. & Murshudov, G.N. Low-resolution refinement tools in REFMAC5. Acta Crystallogr. D Biol. Crystallogr. 68, 404\u2013417 (2012).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"BFnsmb3343_CR65","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1126\/science.1249410","volume":"343","author":"A Amunts","year":"2014","unstructured":"Amunts, A. et al. Structure of the yeast mitochondrial large ribosomal subunit. Science 343, 1485\u20131489 (2014).","journal-title":"Science"},{"key":"BFnsmb3343_CR66","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"W Kabsch","year":"2010","unstructured":"Kabsch, W. Xds. Acta Crystallogr. D Biol. Crystallogr. 66, 125\u2013132 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"BFnsmb3343_CR67","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1107\/S0907444905036693","volume":"62","author":"P Evans","year":"2006","unstructured":"Evans, P. Scaling and assessment of data quality. Acta Crystallogr. D Biol. Crystallogr. 62, 72\u201382 (2006).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"BFnsmb3343_CR68","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P.D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"BFnsmb3343_CR69","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1113\/jphysiol.1991.sp018481","volume":"434","author":"R Sitsapesan","year":"1991","unstructured":"Sitsapesan, R., Montgomery, R.A., MacLeod, K.T. & Williams, A.J. Sheep cardiac sarcoplasmic reticulum calcium-release channels: modification of conductance and gating by temperature. J. Physiol. (Lond.) 434, 469\u2013488 (1991).","journal-title":"J. Physiol. (Lond.)"},{"key":"BFnsmb3343_CR70","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1007\/s00249-011-0715-2","volume":"40","author":"MR Cantero","year":"2011","unstructured":"Cantero, M.R. & Cantiello, H.F. Effect of lithium on the electrical properties of polycystin-2 (TRPP2). Eur. Biophys. J. 40, 1029\u20131042 (2011).","journal-title":"Eur. Biophys. J."},{"key":"BFnsmb3343_CR71","doi-asserted-by":"publisher","first-page":"16901","DOI":"10.1073\/pnas.1412689111","volume":"111","author":"L Moparthi","year":"2014","unstructured":"Moparthi, L. et al. Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain. Proc. Natl. Acad. Sci. USA 111, 16901\u201316906 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnsmb3343_CR72","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/978-1-60327-058-8_8","volume":"426","author":"N Eswar","year":"2008","unstructured":"Eswar, N., Eramian, D., Webb, B., Shen, M.Y. & Sali, A. Protein structure modeling with MODELLER. Methods Mol. Biol. 426, 145\u2013159 (2008).","journal-title":"Methods Mol. Biol."},{"key":"BFnsmb3343_CR73","unstructured":"Schrodinger, LLC. The JyMOL Molecular Graphics Development Component, Version 1.0 (2010)."},{"key":"BFnsmb3343_CR74","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E.F. et al. UCSF Chimera: a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605\u20131612 (2004).","journal-title":"J. Comput. Chem."},{"key":"BFnsmb3343_CR75","doi-asserted-by":"publisher","first-page":"W665","DOI":"10.1093\/nar\/gkh381","volume":"32","author":"TJ Dolinsky","year":"2004","unstructured":"Dolinsky, T.J., Nielsen, J.E., McCammon, J.A. & Baker, N.A. PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations. Nucleic Acids Res. 32, W665\u2013W667 (2004).","journal-title":"Nucleic Acids Res."}],"container-title":["Nature Structural &amp; Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nsmb.3343.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nsmb.3343","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nsmb.3343.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T04:41:05Z","timestamp":1684471265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nsmb.3343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,19]]},"references-count":75,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["BFnsmb3343"],"URL":"https:\/\/doi.org\/10.1038\/nsmb.3343","relation":{},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,19]]},"assertion":[{"value":"5 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}