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-Structure paper
タイトル | Ca-induced movement of tropomyosin on native cardiac thin filaments revealed by cryoelectron microscopy. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 114, Issue 26, Page 6782-6787, Year 2017 |
掲載日 | 2017年6月27日 |
著者 | Cristina Risi / Jamie Eisner / Betty Belknap / David H Heeley / Howard D White / Gunnar F Schröder / Vitold E Galkin / |
PubMed 要旨 | 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 Ca The current model of ...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 Ca The current model of muscle regulation holds that at relaxing (low-Ca) conditions tropomyosin blocks myosin binding sites on F-actin, whereas at activating (high-Ca) 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 Ca 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 Ca, 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 Ca and lead to a mechanistic model for the regulation of the cardiac TF. |
リンク | Proc Natl Acad Sci U S A / PubMed:28607071 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 8.0 - 11.0 Å |
構造データ | EMDB-3665, PDB-5nog: |
化合物 | ChemComp-ADP: ChemComp-MG: |
由来 |
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キーワード | MOTOR PROTEIN (モータータンパク質) / F-actin (アクチン) / tropomyosin (トロポミオシン) |