PDBsum entry 2mkp

Metal binding protein

PDB id: 2mkp

Contents

Protein chains

89 a.a.

17 a.a.

Metals

_CA

PDB id:

2mkp

Name:

Metal binding protein

Title:

N domain of cardiac troponin c bound to the switch fragment of fast skeletal troponin i at ph 6

Structure:

Troponin c, slow skeletal and cardiac muscles. Chain: c. Fragment: unp residues 1-89. Synonym: tn-c. Engineered: yes. Troponin i, fast skeletal muscle. Chain: i. Fragment: unp residues 116-132. Synonym: troponin i, fast-twitch isoform.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tnnc1, tnnc. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: tnni2. Expression_system_taxid: 562

NMR struc:

10 models

Authors:

I.M.Robertson,S.E.Pineda-Sanabria,P.C.Holmes,B.D.Sykes

Key ref:

I.M.Robertson et al. (2014). Conformation of the critical pH sensitive region of troponin depends upon a single residue in troponin I. Arch Biochem Biophys, 552, 40-49. PubMed id: 24333682 DOI: 10.1016/j.abb.2013.12.003

Date:

11-Feb-14 Release date: 26-Feb-14

Protein chain

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

Seq: 161 a.a.

Struc: 89 a.a.

Protein chain

P48788  (TNNI2_HUMAN) -  Troponin I, fast skeletal muscle from Homo sapiens

Seq: 182 a.a.

Struc: 17 a.a.

DOI no: 10.1016/j.abb.2013.12.003

Arch Biochem Biophys 552:40-49 (2014)

PubMed id: 24333682

Conformation of the critical pH sensitive region of troponin depends upon a single residue in troponin I.

I.M.Robertson, S.E.Pineda-Sanabria, P.C.Holmes, B.D.Sykes.

ABSTRACT

The calcium sensitivity of cardiac and skeletal muscle is reduced during cytosolic acidosis, and this inhibition is more pronounced in cardiac muscle. Replacing cardiac troponin I with skeletal troponin I reduces the pH sensitivity of cardiac muscle. This diminished pH sensitivity depends on a single amino acid difference in troponin I: an alanine in cardiac and a histidine in skeletal. Studies suggested that when this histidine is protonated, it forms an electrostatic interaction with glutamate 19 on the surface of cardiac troponin C. Structures of the skeletal and cardiac troponin complexes show very different conformations for the region of troponin I surrounding this residue. In this study, we determined the structure of skeletal troponin I bound to cardiac troponin C. Skeletal troponin I is found to bind to cardiac troponin C with histidine 130 in close proximity to glutamate 19. This conformation is homologous to the crystal structure of the skeletal troponin complex; but different than in the cardiac complex. We show that an A162H variant of cardiac troponin I adopts a conformation similar to the skeletal structure. The implications of these structural differences in the context of cardiac muscle regulation are discussed.