PDBsum entry 2ctn

Calcium-binding protein

PDB id: 2ctn

Contents

Protein chain

88 a.a. *

Metals

_CA

* Residue conservation analysis

PDB id:

2ctn

Name:

Calcium-binding protein

Title:

Structure of calcium-saturated cardiac troponin c, nmr, 30 structures

Structure:

Troponin c. Chain: a. Fragment: regulatory n-domain residues 2 - 89. Synonym: ctnc. Engineered: yes. Mutation: yes. Other_details: cardiac troponin c with calcium ion bound at site ii

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Cell_line: bl21. Organ: heart. Tissue: muscle. Cellular_location: thin filament. Gene: ctnc(a-cys). Expressed in: escherichia coli.

NMR struc:

30 models

Authors:

S.K.Sia,M.X.Li,L.Spyracopoulos,S.M.Gagne,W.Liu,J.A.Putkey,B.D.Sykes

Key ref:

S.K.Sia et al. (1997). Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain. J Biol Chem, 272, 18216-18221. PubMed id: 9218458 DOI: 10.1074/jbc.272.29.18216

Date:

06-May-97 Release date: 06-May-98

Protein chain

P09860  (TNNC1_CHICK) -  Troponin C, slow skeletal and cardiac muscles from Gallus gallus

Seq: 161 a.a.

Struc: 88 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1074/jbc.272.29.18216

J Biol Chem 272:18216-18221 (1997)

PubMed id: 9218458

Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain.

S.K.Sia, M.X.Li, L.Spyracopoulos, S.M.Gagné, W.Liu, J.A.Putkey, B.D.Sykes.

ABSTRACT

The regulation of cardiac muscle contraction must differ from that of skeletal muscles to effect different physiological and contractile properties. Cardiac troponin C (TnC), the key regulator of cardiac muscle contraction, possesses different functional and Ca2+-binding properties compared with skeletal TnC and features a Ca2+-binding site I, which is naturally inactive. The structure of cardiac TnC in the Ca2+-saturated state has been determined by nuclear magnetic resonance spectroscopy. The regulatory domain exists in a "closed" conformation even in the Ca2+-bound (the "on") state, in contrast to all predicted models and differing significantly from the calcium-induced structure observed in skeletal TnC. This structure in the Ca2+-bound state, and its subsequent interaction with troponin I (TnI), are crucial in determining the specific regulatory mechanism for cardiac muscle contraction. Further, it will allow for an understanding of the action of calcium-sensitizing drugs, which bind to cardiac TnC and are known to enhance the ability of cardiac TnC to activate cardiac muscle contraction.

Selected figure(s)

Figure 1.
Fig. 1. Structure of Ca^2+-saturated cardiac TnC as determined in this study (sequence starts at Ala^2 and ends at Val161). The -helices are approximately as follows: N-helix (residues 6-10), A-helix (14-28), B-helix (38-48), C-helix (54-64), D-helix (74-83), E-helix (95-103), F-helix (114-123), G-helix (130-140), H-helix (150-158). The antiparallel -sheets connect residues 35-37 and 71-73 in the N-domain, and residues 111-113 and 147-149^ in the C-domain. All regions of the molecule are well defined, with the exceptions of the following regions: the N- and C-terminal residues (2-4 and 159-161), residues 30-33 of defunct site I, residues 49-55 of the B-C linker, residues 66-68 of site II, the^ central linker (86-94), and residues 125-129 of the F-G linker. Stereo views of the superposition of 30 structures for the regulatory N-domain (residues 5-84, A) and the structural C-domain (95-158, B) are shown. Positions of the Ca^2+ ions are indicated by gray spheres. This figure was prepared^ with the program RASTER3D (37).

Figure 4.
Fig. 4. Comparison of the surface structures of the regulatory N-domains of 4Ca·skeletal TnC (NMR) (A), 3Ca·cardiac TnC (NMR) (B), and 3Ca·cardiac TnC (model, Ref. 9) (C), displayed in the same^ orientation as Fig. 1A. Side chains of hydrophobic residues (Ala, Ile, Leu, Met, Pro, Phe, Tyr, and Val) are shown in yellow, negatively charged residues (Asp and Glu) in red, positively charged^ residues (Arg and Lys) in blue, and all other residues in gray. The major hydrophobic pocket of 3Ca·cardiac TnC involves residues Phe^20, Phe^24, Leu48, Phe^74, Phe^77, Leu78, Met81, and Met85, and residues Ile^36, Leu41, Met45, Leu57, Met60, Ile^61, Val64, Val72, and Met80. Other hydrophobic contacts are also observed from Phe^20, Ala^23, and Phe^27 of the A-helix to Val44, Met47, and Leu48 of the B-helix, and from Ala^8, Val9, and Leu12 of the N-helix to Leu78, Val79, and Val82 of the D-helix. This figure was generated using the program GRASP (38).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1997, 272, 18216-18221) copyright 1997.

Figures were selected by an automated process.