{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:55:23Z","timestamp":1783515323316,"version":"3.55.0"},"reference-count":58,"publisher":"Rockefeller University Press","issue":"3","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":217,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL124091"],"award-info":[{"award-number":["HL124091"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL 063774"],"award-info":[{"award-number":["HL 063774"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:p>Reversible Ca2+ binding to troponin is the primary on-off switch of the contractile apparatus of striated muscles, including the heart. Dominant missense mutations in human cardiac troponin genes are among the causes of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy. Structural understanding of troponin action has recently advanced considerably via electron microscopy and molecular dynamics studies of the thin filament. As a result, it is now possible to examine cardiomyopathy-inducing troponin mutations in thin-filament structural context, and from that to seek new insight into pathogenesis and into the troponin regulatory mechanism. We compiled from consortium reports a representative set of troponin mutation sites whose pathogenicity was determined using standardized clinical genetics criteria. Another set of sites, apparently tolerant of amino acid substitutions, was compiled from the gnomAD v2 database. Pathogenic substitutions occurred predominantly in the areas of troponin that contact actin or tropomyosin, including, but not limited to, two regions of newly proposed structure and long-known implication in cardiomyopathy: the C-terminal third of troponin I and a part of the troponin T N terminus. The pathogenic mutations were located in troponin regions that prevent contraction under low Ca2+ concentration conditions. These regions contribute to Ca2+-regulated steric hindrance of myosin by the combined effects of troponin and tropomyosin. Loss-of-function mutations within these parts of troponin result in loss of inhibition, consistent with the hypercontractile phenotype characteristic of HCM. Notably, pathogenic mutations are absent in our dataset from the Ca2+-binding, activation-producing troponin C (TnC) N-lobe, which controls contraction by a multi-faceted mechanism. Apparently benign mutations are also diminished in the TnC N-lobe, suggesting mutations are poorly tolerated in that critical domain.<\/jats:p>","DOI":"10.1085\/jgp.202012815","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T01:43:13Z","timestamp":1611625393000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Cardiomyopathic troponin mutations predominantly occur at its interface with actin and tropomyosin"],"prefix":"10.1085","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1461-5765","authenticated-orcid":true,"given":"Larry S.","family":"Tobacman","sequence":"first","affiliation":[{"name":"Departments of Medicine and of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Cammarato","sequence":"additional","affiliation":[{"name":"Departments of Medicine and of Physiology, Johns Hopkins University, Baltimore, MD 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"2023072711254389700_bib1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24634","article-title":"Effects of myosin variants on interacting-heads motif explain distinct hypertrophic and dilated cardiomyopathy phenotypes","volume":"6","author":"Alamo","year":"2017","journal-title":"eLife."},{"key":"2023072711254389700_bib2","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/gim.2014.205","article-title":"Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity","volume":"17","author":"Alfares","year":"2015","journal-title":"Genet. Med."},{"key":"2023072711254389700_bib3","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1006\/bbrc.1997.7045","article-title":"Effects of two hypertrophic cardiomyopathy mutations in alpha-tropomyosin, Asp175Asn and Glu180Gly, on Ca2+ regulation of thin filament motility","volume":"236","author":"Bing","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023072711254389700_bib4","doi-asserted-by":"crossref","unstructured":"Burbaum, L., J.Schneider, S.Scholze, R.T.B\u00f6ttcher, W.Baumeister, P.Schwille, J.M.Plitzko, and M.Jasnin. 2020. Molecular-scale visualization of sarcomere contraction within native cardiomyocytes. bioRxiv. https:\/\/doi.org\/10.1101\/2020.09.09.288977 (Preprint posted September 9, 2020).","DOI":"10.1101\/2020.09.09.288977"},{"key":"2023072711254389700_bib5","doi-asserted-by":"publisher","first-page":"27749","DOI":"10.1074\/jbc.M115.683045","article-title":"Troponin I Mutations R146G and R21C Alter Cardiac Troponin Function, Contractile Properties, and Modulation by Protein Kinase A (PKA)-mediated Phosphorylation","volume":"290","author":"Cheng","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib6","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.bpj.2020.07.006","article-title":"Cryo-EM and Molecular Docking Shows Myosin Loop 4 Contacts Actin and Tropomyosin on Thin Filaments","volume":"119","author":"Doran","year":"2020","journal-title":"Biophys. J."},{"key":"2023072711254389700_bib7","doi-asserted-by":"publisher","first-page":"21817","DOI":"10.1074\/jbc.M116.746172","article-title":"Restrictive Cardiomyopathy Troponin I R145W Mutation Does Not Perturb Myofilament Length-dependent Activation in Human Cardiac Sarcomeres","volume":"291","author":"Dvornikov","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib8","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1093\/oxfordjournals.jbchem.a128628","article-title":"Troponin as the Ca++-receptive protein in the contractile system","volume":"62","author":"Ebashi","year":"1967","journal-title":"J. Biochem."},{"key":"2023072711254389700_bib9","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1161\/01.CIR.94.12.3069","article-title":"Codon 102 of the cardiac troponin T gene is a putative hot spot for mutations in familial hypertrophic cardiomyopathy","volume":"94","author":"Forissier","year":"1996","journal-title":"Circulation."},{"key":"2023072711254389700_bib10","doi-asserted-by":"publisher","first-page":"11115","DOI":"10.1073\/pnas.1710354114","article-title":"Molecular mechanisms and structural features of cardiomyopathy-causing troponin T mutants in the tropomyosin overlap region","volume":"114","author":"Gangadharan","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072711254389700_bib11","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/0092-8674(90)90274-I","article-title":"A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation","volume":"62","author":"Geisterfer-Lowrance","year":"1990","journal-title":"Cell."},{"key":"2023072711254389700_bib12","doi-asserted-by":"publisher","first-page":"H884","DOI":"10.1152\/ajpheart.00528.2014","article-title":"The functional effect of dilated cardiomyopathy mutation (R144W) in mouse cardiac troponin T is differently affected by \u03b1- and \u03b2-myosin heavy chain isoforms","volume":"308","author":"Gollapudi","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2023072711254389700_bib13","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1152\/physrev.2000.80.2.853","article-title":"Regulation of contraction in striated muscle","volume":"80","author":"Gordon","year":"2000","journal-title":"Physiol. Rev."},{"key":"2023072711254389700_bib14","doi-asserted-by":"publisher","first-page":"14488","DOI":"10.1074\/jbc.M309355200","article-title":"Familial hypertrophic cardiomyopathy mutations from different functional regions of troponin T result in different effects on the pH and Ca2+ sensitivity of cardiac muscle contraction","volume":"279","author":"Harada","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib15","doi-asserted-by":"publisher","first-page":"41742","DOI":"10.1074\/jbc.M303408200","article-title":"Cardiomyopathic tropomyosin mutations that increase thin filament Ca2+ sensitivity and tropomyosin N-domain flexibility","volume":"278","author":"Heller","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib16","doi-asserted-by":"publisher","first-page":"7157","DOI":"10.1074\/jbc.274.11.7157","article-title":"Roles for the troponin tail domain in thin filament assembly and regulation. A deletional study of cardiac troponin T","volume":"274","author":"Hinkle","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib17","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1161\/CIRCULATIONAHA.117.033200","article-title":"Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe)","volume":"138","author":"Ho","year":"2018","journal-title":"Circulation."},{"key":"2023072711254389700_bib18","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1101\/SQB.1973.037.01.046","article-title":"Structural changes in the actin and myosin containing filaments during contraction","volume":"37","author":"Huxley","year":"1972","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"2023072711254389700_bib19","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.abb.2010.06.001","article-title":"Localization of the two tropomyosin-binding sites of troponin T","volume":"500","author":"Jin","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"2023072711254389700_bib20","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature."},{"key":"2023072711254389700_bib21","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/ng0897-379","article-title":"Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy","volume":"16","author":"Kimura","year":"1997","journal-title":"Nat. Genet."},{"key":"2023072711254389700_bib22","doi-asserted-by":"publisher","first-page":"13471","DOI":"10.1074\/jbc.M509561200","article-title":"Increased Ca2+ affinity of cardiac thin filaments reconstituted with cardiomyopathy-related mutant cardiac troponin I","volume":"281","author":"Kobayashi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib23","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1152\/physiolgenomics.00101.2002","article-title":"Familial hypertrophic cardiomyopathy mutations in troponin I (K183D, G203S, K206Q) enhance filament sliding","volume":"14","author":"K\u00f6hler","year":"2003","journal-title":"Physiol. Genomics."},{"key":"2023072711254389700_bib24","doi-asserted-by":"publisher","first-page":"18822","DOI":"10.1073\/pnas.2001692117","article-title":"TNNT2 mutations in the tropomyosin binding region of TNT1 disrupt its role in contractile inhibition and stimulate cardiac dysfunction","volume":"117","author":"Madan","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072711254389700_bib25","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.jmb.2012.05.008","article-title":"Molecular effects of familial hypertrophic cardiomyopathy-related mutations in the TNT1 domain of cTnT","volume":"421","author":"Manning","year":"2012","journal-title":"J. Mol. Biol."},{"key":"2023072711254389700_bib26","doi-asserted-by":"publisher","first-page":"29774","DOI":"10.1074\/jbc.M201761200","article-title":"A modulatory role for the troponin T tail domain in thin filament regulation","volume":"277","author":"Maytum","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib27","doi-asserted-by":"publisher","first-page":"3403","DOI":"10.1021\/acs.biochem.7b00266","article-title":"Clinically Divergent Mutation Effects on the Structure and Function of the Human Cardiac Tropomyosin Overlap","volume":"56","author":"McConnell","year":"2017","journal-title":"Biochemistry."},{"key":"2023072711254389700_bib28","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/S0006-3495(93)81110-X","article-title":"Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament","volume":"65","author":"McKillop","year":"1993","journal-title":"Biophys. J."},{"key":"2023072711254389700_bib29","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1038\/70990","article-title":"Direct, convergent hypersensitivity of calcium-activated force generation produced by hypertrophic cardiomyopathy mutant alpha-tropomyosins in adult cardiac myocytes","volume":"5","author":"Michele","year":"1999","journal-title":"Nat. Med."},{"key":"2023072711254389700_bib30","doi-asserted-by":"publisher","first-page":"28498","DOI":"10.1074\/jbc.M412281200","article-title":"Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype","volume":"280","author":"Mirza","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib31","doi-asserted-by":"publisher","first-page":"7200","DOI":"10.1073\/pnas.0801950105","article-title":"Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T","volume":"105","author":"Murakami","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072711254389700_bib32","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nsmb.3408","article-title":"The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations","volume":"24","author":"Nag","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2023072711254389700_bib33","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1016\/0022-2828(95)90026-8","article-title":"Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy","volume":"27","author":"Nakajima-Taniguchi","year":"1995","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023072711254389700_bib34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2020.107450","article-title":"Cryo-EM structures of cardiac thin filaments reveal the 3D architecture of troponin","volume":"209","author":"Oda","year":"2020","journal-title":"J. Struct. Biol."},{"key":"2023072711254389700_bib35","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1016\/S0006-3495(01)75924-3","article-title":"Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region","volume":"81","author":"Palm","year":"2001","journal-title":"Biophys. J."},{"key":"2023072711254389700_bib36","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.bpj.2020.05.017","article-title":"Protein-Protein Docking Reveals Dynamic Interactions of Tropomyosin on Actin Filaments","volume":"119","author":"Pavadai","year":"2020","journal-title":"Biophys. J."},{"key":"2023072711254389700_bib37","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.bpj.2019.11.3393","article-title":"Docking Troponin T onto the Tropomyosin Overlapping Domain of Thin Filaments","volume":"118","author":"Pavadai","year":"2020","journal-title":"Biophys. J."},{"key":"2023072711254389700_bib38","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"2023072711254389700_bib39","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1161\/CIRCRESAHA.107.156380","article-title":"Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments","volume":"101","author":"Robinson","year":"2007","journal-title":"Circ. Res."},{"key":"2023072711254389700_bib40","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1161\/01.CIR.91.2.532","article-title":"Molecular basis of familial cardiomyopathies","volume":"91","author":"Schwartz","year":"1995","journal-title":"Circulation."},{"key":"2023072711254389700_bib41","doi-asserted-by":"publisher","first-page":"632","DOI":"10.3389\/fphys.2016.00632","article-title":"Myofilament Calcium Sensitivity: Consequences of the Effective Concentration of Troponin I","volume":"7","author":"Siddiqui","year":"2016","journal-title":"Front. Physiol."},{"key":"2023072711254389700_bib42","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1074\/jbc.275.1.624","article-title":"Altered regulation of cardiac muscle contraction by troponin T mutations that cause familial hypertrophic cardiomyopathy","volume":"275","author":"Szczesna","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib43","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1016\/S0021-9258(19)69684-5","article-title":"Synthetic studies on the inhibitory region of rabbit skeletal troponin I. Relationship of amino acid sequence to biological activity","volume":"256","author":"Talbot","year":"1981","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib44","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1161\/CIRCRESAHA.110.224170","article-title":"Thin filament mutations: developing an integrative approach to a complex disorder","volume":"108","author":"Tardiff","year":"2011","journal-title":"Circ. Res."},{"key":"2023072711254389700_bib45","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/0092-8674(94)90054-X","article-title":"Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere","volume":"77","author":"Thierfelder","year":"1994","journal-title":"Cell."},{"key":"2023072711254389700_bib46","doi-asserted-by":"publisher","first-page":"4651","DOI":"10.1113\/JP276296","article-title":"Desensitizing mouse cardiac troponin C to calcium converts slow muscle towards a fast muscle phenotype","volume":"596","author":"Tikunova","year":"2018","journal-title":"J. Physiol."},{"key":"2023072711254389700_bib47","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1146\/annurev.ph.58.030196.002311","article-title":"Thin filament-mediated regulation of cardiac contraction","volume":"58","author":"Tobacman","year":"1996","journal-title":"Annu. Rev. Physiol."},{"key":"2023072711254389700_bib48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bpj.2020.11.014","article-title":"Troponin revealed: Uncovering the structure of the thin filament on-off switch in striated muscle","volume":"120","author":"Tobacman","year":"2021","journal-title":"Biophys. J"},{"key":"2023072711254389700_bib49","doi-asserted-by":"publisher","first-page":"27636","DOI":"10.1074\/jbc.M201768200","article-title":"The troponin tail domain promotes a conformational state of the thin filament that suppresses myosin activity","volume":"277","author":"Tobacman","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2023072711254389700_bib50","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1006\/jmbi.1996.0800","article-title":"Steric-model for activation of muscle thin filaments","volume":"266","author":"Vibert","year":"1997","journal-title":"J. Mol. Biol."},{"key":"2023072711254389700_bib51","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/gim.2016.90","article-title":"Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples","volume":"19","author":"Walsh","year":"2017","journal-title":"Genet. Med."},{"key":"2023072711254389700_bib52","doi-asserted-by":"crossref","unstructured":"Wang, Z., M.Grange, T.Wagner, A.L.Kho, M.Gautel, and S.Raunser. 2020. Molecular plasticity of the native mouse skeletal sarcomere revealed by cryo-ET. bioRxiv. https:\/\/doi.org\/10.1101\/2020.09.13.295386 (Preprint posted September 13, 2020)","DOI":"10.1101\/2020.09.13.295386"},{"key":"2023072711254389700_bib53","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1056\/NEJMra0902923","article-title":"Inherited cardiomyopathies","volume":"364","author":"Watkins","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"2023072711254389700_bib54","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/ng1295-434","article-title":"Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy","volume":"11","author":"Watkins","year":"1995","journal-title":"Nat. Genet."},{"key":"2023072711254389700_bib55","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1056\/NEJM199504203321603","article-title":"Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy","volume":"332","author":"Watkins","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"2023072711254389700_bib56","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/325826a0","article-title":"Structure of co-crystals of tropomyosin and troponin","volume":"325","author":"White","year":"1987","journal-title":"Nature."},{"key":"2023072711254389700_bib57","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/s41467-019-14008-1","article-title":"Cardiac muscle thin filament structures reveal calcium regulatory mechanism","volume":"11","author":"Yamada","year":"2020","journal-title":"Nat. Commun."},{"key":"2023072711254389700_bib58","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s10974-016-9447-3","article-title":"Investigating the effects of tropomyosin mutations on its flexibility and interactions with filamentous actin using molecular dynamics simulation","volume":"37","author":"Zheng","year":"2016","journal-title":"J. Muscle Res. Cell Motil."}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202012815\/1810254\/jgp_202012815.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202012815\/1810254\/jgp_202012815.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T11:26:43Z","timestamp":1690457203000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/153\/3\/e202012815\/211713\/Cardiomyopathic-troponin-mutations-predominantly"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,25]]},"references-count":58,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.202012815","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,25]]},"article-number":"e202012815"}}