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Specifically, we studied the effects of A57G on the super\u2010relaxed (SRX) state of myosin that may contribute to the hypercontractile cross\u2010bridge behavior and ultimately lead to pathological cardiac remodeling in transgenic Tg\u2010A57G mice. The disease model was compared to Tg\u2010WT mice, expressing the wild\u2010type human ventricular ELC, and analyzed against Tg\u2010\u039443 mice, expressing the N\u2010terminally truncated ELC, whose hearts hypertrophy with time but do not show any abnormalities in cardiac morphology or function. Our data suggest a new role for the N terminus of cardiac ELC (N\u2010ELC) in modulation of myosin cross\u2010bridge function in the healthy as well as in HCM myocardium. The lack of N\u2010ELC in Tg\u2010\u039443 mice was found to significantly stabilize the SRX state of myosin and increase the number of myosin heads occupying a low\u2010energy state. In agreement, \u039443 hearts showed significantly decreased ATP utilization and low actin\u2010activated myosin ATPase compared with A57G and WT hearts. The hypercontractile activity of A57G\u2010ELC cross\u2010bridges was manifested by the inhibition of the SRX state, increased number of myosin heads available for interaction with actin, and higher ATPase activity. Fiber mechanics studies, echocardiography examination, and assessment of fibrosis confirmed the development of two distinct forms of cardiac remodeling in these two ELC mouse models, with pathological cardiac hypertrophy in Tg\u2010A57G, and near physiologic cardiac growth in Tg\u2010\u039443 animals.<\/jats:p>","DOI":"10.1111\/febs.15243","type":"journal-article","created":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T15:02:23Z","timestamp":1581174143000},"page":"3989-4004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Ablation of the N terminus of cardiac essential light chain promotes the super\u2010relaxed state of myosin and counteracts hypercontractility in hypertrophic cardiomyopathy mutant mice"],"prefix":"10.1111","volume":"287","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6460-6421","authenticated-orcid":false,"given":"Yoel 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