TY - JOUR
T1 - Structure of the core domain of human cardiac troponin in the Ca2+-saturated form
AU - Takeda, Soichi
AU - Yamashita, Atsuko
AU - Maeda, Kayo
AU - Maéda, Yuichiro
N1 - Funding Information:
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.
PY - 2003/7/3
Y1 - 2003/7/3
N2 - 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.
AB - 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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U2 - 10.1038/nature01780
DO - 10.1038/nature01780
M3 - Article
C2 - 12840750
AN - SCOPUS:0037588762
VL - 424
SP - 35
EP - 41
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6944
ER -