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- W2002065596 abstract "Along with calcium binding, association of the switch region of troponin I (TnI) to the regulatory N-domain of troponin C (NTnC) is a key step in the regulation of contraction in cardiac and skeletal muscle. The TnI-NTnC interaction has been structurally characterized and the orientation of the switch region of TnI relative to NTnC is known to be very similar for cardiac and skeletal muscle; however, the region of TnI immediately following in the sequence differs substantially and is involved in the differential pH sensitivity of myocytes and cardiomyocyte observed during ischaemia. A single amino acid substitution (A162H, the histidine button) in the acidosis-sensitive cardiac TnI turns the cardiac muscle into the acidosis-resistant phenotype of skeletal muscle. The cause of this improvement is attributed to electrostatic interactions promoted by the histidine button in TnI with NTnC, but little is known about the structural characteristics of this system. In this study, we used NMR spectroscopy to determine the conformation of the pH-sensitive region of cardiac TnI A162H and skeletal TnI when bound to cardiac NTnC at pH 6. The results show that the pH-sensitive regions of both isoforms are in very similar conformations and resemble the conformation of the skeletal TnI when bound to skeletal NTnC. This indicates that the histidine, and not the NTnC isoform or other TnI residues, is the main determinant of the conformation of the pH sensitive region of TnI. The promotion of a conformational change in cardiac TnI in the presence of A162H at low pH then leads to the stabilization of TnI and of the TnI-NTnC interface to continue the contraction mechanism in the face of acidosis." @default.
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- W2002065596 date "2014-01-01" @default.
- W2002065596 modified "2023-09-27" @default.
- W2002065596 title "The Histidine Button Dictates the Conformation of the pH-Sensitive Region of Troponin I" @default.
- W2002065596 doi "https://doi.org/10.1016/j.bpj.2013.11.2644" @default.
- W2002065596 hasPublicationYear "2014" @default.
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