Biomaterial Database

Calcium binding to skeletal muscle troponin C and the regulation of muscle contraction. 1986

O Herzberg, and J Moult, and M N James

Skeletal muscle contraction is initiated by Ca2+ ion binding to troponin C (TnC), a protein of the thin filament. Our three-dimensional structure determination of turkey skeletal TnC at 2.8 A resolution revealed an extended molecule consisting of two domains connected through a long nine-turn alpha-helix. The C-terminal domain has two Ca2+ ions bound in the expected manner of EF hands, whereas the N-terminal regulatory domain is Ca2+-free with a helix-loop-helix conformation different from that of an EF hand. The refinement of TnC at 2.2 A resolution highlights the intricate hydrogen-bonded network common to the Ca2+-bound loops and provides an explanation for the presence of a water molecule in the 5th coordination position of the Ca2+ ion. We propose that Ca2+ binding to the regulatory domain is accompanied by a conformational transition by which its structure becomes similar to that of the C-terminal domain. Dramatic movements of residues in the B and C helices and the connecting peptide of up to 14 A constitute the bulk of this change. A hydrophobic site that could be the site of interaction with troponin I is thereby exposed. We have also demonstrated that this model of the Ca2+-bound conformation can be reached from the Ca2+-free state without having to surmount large energy barriers.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009132	Muscles	Contractile tissue that produces movement in animals.	Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006860	Hydrogen Bonding	A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.	Hydrogen Bonds,Bond, Hydrogen,Hydrogen Bond
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014336	Troponin	One of the minor protein components of skeletal and cardiac muscles. It functions as the calcium-binding component in a complex with BETA-TROPOMYOSIN; ACTIN; and MYOSIN and confers calcium sensitivity to the cross-linked actin and myosin filaments. Troponin itself is a complex of three regulatory proteins (TROPONIN C; TROPONIN I; and TROPONIN T).	Troponin Complex,Troponins