文章基本信息

标题：Ca2+-induced movement of tropomyosin on native cardiac thin filaments revealed by cryoelectron microscopy
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作者：Cristina Risi ; Jamie Eisner ; Betty Belknap 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：26
页码：6782-6787
DOI：10.1073/pnas.1700868114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Muscle contraction relies on the interaction of myosin motors with F-actin, which is regulated through a translocation of tropomyosin by the troponin complex in response to Ca²⁺. The current model of muscle regulation holds that at relaxing (low-Ca²⁺) conditions tropomyosin blocks myosin binding sites on F-actin, whereas at activating (high-Ca²⁺) conditions tropomyosin translocation only partially exposes myosin binding sites on F-actin so that binding of rigor myosin is required to fully activate the thin filament (TF). Here we used a single-particle approach to helical reconstruction of frozen hydrated native cardiac TFs under relaxing and activating conditions to reveal the azimuthal movement of the tropomyosin on the surface of the native cardiac TF upon Ca²⁺ activation. We demonstrate that at either relaxing or activating conditions tropomyosin is not constrained in one structural state, but rather is distributed between three structural positions on the surface of the TF. We show that two of these tropomyosin positions restrain actomyosin interactions, whereas in the third position, which is significantly enhanced at high Ca²⁺, tropomyosin does not block myosin binding sites on F-actin. Our data provide a structural framework for the enhanced activation of the cardiac TF over the skeletal TF by Ca²⁺ and lead to a mechanistic model for the regulation of the cardiac TF.
关键词：thin filament ; cardiac muscle regulation ; cryoelectron microscopy