Crossbridge Recruitment Capacity of Wild-Type and Hypertrophic Cardiomyopathy-Related Mutant Troponin-T Evaluated by X-ray Diffraction and Mechanical Study of Cardiac Skinned Fibers.

Abstract

X-ray diffraction and tension measurement experiments were conducted on rat left ventricular skinned fibers with or without "troponin-T treatment," which exchanges the endogenous troponin T/I/C complex with exogenous troponin-T. These experiments were performed to observe the structural changes in troponin-T within a fiber elicited by contractile crossbridge formation and investigate the abnormality of hypertrophic cardiomyopathy-related troponin-T mutants. The intensity of the troponin reflection at 1/38.5 nm-1 was decreased significantly by ATP addition after treatment with wild-type or mutant troponin-T, indicating that crossbridge formation affected the conformation of troponin-T. In experiments on cardiac fibers treated with the hypertrophic cardiomyopathy-related mutants E244D- and K247R-troponin-T, treatment with K247R-troponin-T did not recruit contracting actomyosin to a greater extent than wild-type-troponin-T, although a similar drop in the intensity of the troponin reflection occurred. Therefore, the conformational change in K247R-troponin-T was suggested to be unable to fully recruit actomyosin interaction, which may be the cause of cardiomyopathy.

• Authors: Maki Yamaguchi, Masako Kimura, Tetsuo Ohno, Naoya Nakahara, Nobutake Akiyama, Shigeru Takemori, Naoto Yagi
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 10 (May 15 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32429250 (Publication Type: Journal Article)

Chemical References

• Troponin T

Topics

• Animals
• Cardiomyopathies (diagnostic imaging, genetics)
• Male
• Mutation (genetics)
• Myocardium (pathology)
• Protein Domains
• Rats, Wistar
• Troponin T (chemistry, genetics)
• X-Ray Diffraction