Crystal structure of troponin and the molecular mechanism of muscle regulation.
Troponin plays a central role in the regulation of skeletal and cardiac muscle contraction. The protein consists of three polypeptide chains (TnT, TnI and TnC) and is located on polymerized actin together with tropomyosin, forming muscle thin filament. We have determined the molecular structures of the core domains (relative molecular mass of 46,000 and 52,000) of human cardiac troponin in the Ca2+-saturated form by X-ray crystallography. Analysis of the four structures derived from the two crystal forms reveals that the core domain is further divided into sub-domains, connected by linkers, making the entire molecule highly flexible. The structures of the troponin ternary complex suggests that the Ca2+-binding to the regulatory TnC site displaces the carboxyl-terminal portion of TnI from actin/tropomyosin, thereby altering mobility and/or flexibility of the troponin/tropomyosin strand on the actin filament. These Ca2+-dependent changes in the properties of the tropomyosin strand on the actin filament may in turn alter accessibility of myosin heads (motor protein) to the actin filament.
Takeda
Soichi
S
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. stakeda@ri.ncvc.go.jp
D002118:Calcium / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D009119:Muscle Contraction / Q000502:physiology*; D009206:Myocardium; D014336:Troponin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D019209:Troponin C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D019210:Troponin I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D020107:Troponin T / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
D014336:Troponin; D019209:Troponin C; D019210:Troponin I; D020107:Troponin T; D002118:Calcium