2MKP

N domain of cardiac troponin C bound to the switch fragment of fast skeletal troponin I at pH 6

Summary for 2MKP

• Entry DOI: 10.2210/pdb2mkp/pdb
• NMR Information: BMRB: 19789
• Descriptor: Troponin C, slow skeletal and cardiac muscles, Troponin I, fast skeletal muscle, CALCIUM ION (3 entities in total)
• Functional Keywords: troponin c, troponin i, ef-hand, calcium binding, ischemia, metal binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 11972.67

Authors

Robertson, I.M.,Pineda-Sanabria, S.E.,Holmes, P.C.,Sykes, B.D. (deposition date: 2014-02-11, release date: 2014-02-26, Last modification date: 2024-05-01)

Primary citation

Robertson, I.M.,Pineda-Sanabria, S.E.,Holmes, P.C.,Sykes, B.D.
Conformation of the critical pH sensitive region of troponin depends upon a single residue in troponin I.
Arch.Biochem.Biophys., 552-553:40-49, 2014

PubMed 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.

PubMed: 24333682
DOI: 10.1016/j.abb.2013.12.003

Experimental method

SOLUTION NMR