Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form.
Troponin is essential in Ca(2+) 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 Ca(2+)-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 alpha-helical coiled-coil formed between TnT and TnI is integrated in a rigid and asymmetric structure (about 80 angstrom long), the IT arm, which bridges putative tropomyosin-anchoring regions. The structures of the troponin ternary complex imply that Ca(2+) 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.
Takeda
Soichi
S
Laboratory for Structural Biochemistry, RIKEN Harima Institute at SPring-8, Mikazuki, Sayo, Hyogo, Japan. stakeda@ri.ncvc.go.jp
Yamashita
Atsuko
A
Maeda
Kayo
K
Maéda
Yuichiro
Y
D002118:Calcium / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D018583:Pliability; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D014335:Tropomyosin / Q000737:chemistry / Q000378:metabolism; D014336:Troponin / Q000737:chemistry* / Q000378:metabolism*; D019209:Troponin C / Q000737:chemistry / Q000378:metabolism; D019210:Troponin I / Q000737:chemistry / Q000378:metabolism; D020107:Troponin T / Q000737:chemistry / Q000378:metabolism
D021122:Protein Subunits; D014335:Tropomyosin; D014336:Troponin; D019209:Troponin C; D019210:Troponin I; D020107:Troponin T; D002118:Calcium