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Structure of the core domain of human cardiac troponin in the Ca2+-saturated form

Nature volume 424, pages 35–41 (2003)Cite this article

Abstract

Troponin is essential in Ca2+ regulation of skeletal and cardiac muscle contraction. It consists of three subunits (TnT, TnC and TnI) and, together with tropomyosin, is located on the actin filament. Here we present crystal structures of the core domains (relative molecular mass of 46,000 and 52,000) of human cardiac troponin in the Ca2+-saturated form. Analysis of the four-molecule structures reveals that the core domain is further divided into structurally distinct subdomains that are connected by flexible linkers, making the entire molecule highly flexible. The α-helical coiled-coil formed between TnT and TnI is integrated in a rigid and asymmetric structure (about 80 Å long), the IT arm, which bridges putative tropomyosin-anchoring regions. The structures of the troponin ternary complex imply that Ca2+ binding to the regulatory site of TnC removes the carboxy-terminal portion of TnI from actin, thereby altering the mobility and/or flexibility of troponin and tropomyosin on the actin filament.

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Figure 1: Crystal structure of the troponin core domain.
Figure 2: Comparison of the four troponin core domain molecules from two crystal forms, Tn46K and Tn52K.
Figure 3: Comparison of the TnC conformations, represented by cylinders (α-helices) and wires (loops).
Figure 4: Side-chain interactions between the subunits.
Figure 5: A schematic representation of the interactions between troponin and other thin filament components.

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Acknowledgements

We thank Y. Kawano, S. Adachi, S.-Y. Park, M. Kawamoto and K. Miura for technical help at the beam lines of SPring-8. We also thank S. Ebashi, I. Ohtsuki, F. Oosawa, K. Maruyama and T. Nitta for continuous support and encouragement throughout this work. This work was supported in part by Matsushita Electric Industrials, and by the Special Coordination Funds from the Ministry of Education, Culture, Sports, Science and Technology, Japan. We dedicate this paper to S. Ebashi.

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  1. Soichi Takeda

    Present address: Department of Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan

Authors and Affiliations

  1. Laboratory for Structural Biochemistry, RIKEN Harima Institute at SPring-8, 1-1-1 Kouto, Mikazuki, Sayo, Hyogo, 679-5148, Japan

    Soichi Takeda, Atsuko Yamashita, Kayo Maeda & Yuichiro Maéda

  2. PRESTO, Japan Science and Technology Corporation (JST), Kawaguchi, Saitama, 332-0012, Japan

    Soichi Takeda

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Takeda, S., Yamashita, A., Maeda, K. et al. Structure of the core domain of human cardiac troponin in the Ca2+-saturated form. Nature 424, 35–41 (2003). https://doi.org/10.1038/nature01780

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