PDBsum entry 4gje

Contractile protein

PDB id: 4gje

Contents

Protein chain

86 a.a.

Ligands

ACT ×3

Metals

_CA ×2

_CD ×7

Waters ×67

PDB id:

4gje

Name:

Contractile protein

Title:

Crystal structure of the refolded amino-terminal domain of human cardiac troponin c in complex with cadmium

Structure:

Troponin c, slow skeletal and cardiac muscles. Chain: a. Fragment: n-terminal domain (unp residues 1-89). Synonym: tn-c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tnnc, tnnc1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.122 R-free: 0.150

Authors:

X.Zhang,M.Paetzel

Key ref:

X.L.Zhang et al. (2013). The structure of cardiac troponin C regulatory domain with bound Cd2+ reveals a closed conformation and unique ion coordination. Acta Crystallogr D Biol Crystallogr, 69, 722-734. PubMed id: 23633581 DOI: 10.1107/S0907444913001182

Date:

09-Aug-12 Release date: 06-Feb-13

Protein chain

P63316  (TNNC1_HUMAN) -  Troponin C, slow skeletal and cardiac muscles from Homo sapiens

Seq: 161 a.a.

Struc: 86 a.a.

DOI no: 10.1107/S0907444913001182

Acta Crystallogr D Biol Crystallogr 69:722-734 (2013)

PubMed id: 23633581

The structure of cardiac troponin C regulatory domain with bound Cd2+ reveals a closed conformation and unique ion coordination.

X.L.Zhang, G.F.Tibbits, M.Paetzel.

ABSTRACT

The amino-terminal domain of cardiac troponin C (cNTnC) is an essential Ca(2+) sensor found in cardiomyocytes. It undergoes a conformational change upon Ca(2+) binding and transduces the signal to the rest of the troponin complex to initiate cardiac muscle contraction. Two classical EF-hand motifs (EF1 and EF2) are present in cNTnC. Under physiological conditions, only EF2 binds Ca(2+); EF1 is a vestigial site that has lost its function in binding Ca(2+) owing to amino-acid sequence changes during evolution. Proteins with EF-hand motifs are capable of binding divalent cations other than calcium. Here, the crystal structure of wild-type (WT) human cNTnC in complex with Cd(2+) is presented. The structure of Cd(2+)-bound cNTnC with the disease-related mutation L29Q, as well as a structure with the residue differences D2N, V28I, L29Q and G30D (NIQD), which have been shown to have functional importance in Ca(2+) sensing at lower temperatures in ectothermic species, have also been determined. The structures resemble the overall conformation of NMR structures of Ca(2+)-bound cNTnC, but differ significantly from a previous crystal structure of Cd(2+)-bound cNTnC in complex with deoxycholic acid. The subtle structural changes observed in the region near the mutations may play a role in the increased Ca(2+) affinity. The 1.4 Å resolution WT cNTnC structure, which is the highest resolution structure yet obtained for cardiac troponin C, reveals a Cd(2+) ion coordinated in the canonical pentagonal bipyramidal geometry in EF2 despite three residues in the loop being disordered. A Cd(2+) ion found in the vestigial ion-binding site of EF1 is coordinated in a noncanonical `distorted' octahedral geometry. A comparison of the ion coordination observed within EF-hand-containing proteins for which structures have been solved in the presence of Cd(2+) is presented. A refolded WT cNTnC structure is also presented.