Evolution, Regulation, and Function of N-terminal Variable Region of Troponin T: Modulation of Muscle Contractility and Beyond - PubMed

Review

Evolution, Regulation, and Function of N-terminal Variable Region of Troponin T: Modulation of Muscle Contractility and Beyond

Jian-Ping Jin. Int Rev Cell Mol Biol. 2016.

Abstract

Troponin T (TnT) is the tropomyosin-binding and thin filament-anchoring subunit of the troponin complex in skeletal and cardiac muscles. At the center of the sarcomeric thin filament regulatory system of striated muscles, TnT plays an essential role in transducing Ca(2+) signals in the regulation of contraction. Having emerged predating the history of vertebrates, TnT has gone through more than 500 million years of evolution that resulted in three muscle-type-specific isoforms and numerous alternative RNA splicing variants. The N-terminal region of TnT is a hypervariable structure responsible for the differences among the TnT isoforms and splice forms. This focused review summarizes our current knowledge of the molecular evolution of the N-terminal variable region and its role in the structure and function of TnT. In addition to the physiologic and pathophysiologic significances in modifying the contractility of skeletal and cardiac muscles during development and in adaptation to stress and disease conditions, the hyperplasticity of the N-terminal region of TnT demonstrates an informative example for the evolution of protein three-dimensional structure and provides insights into the molecular evolution and functional potential of proteins.

Keywords: N-terminal variable region; alternative splicing; calcium regulation of contraction; molecular evolution; protein conformation; proteolytic modification; striated muscle thin filament; troponin T isoforms.

Similar articles

• N-Terminal Hypervariable Region of Muscle Type Isoforms of Troponin T Differentially Modulates the Affinity of Tropomyosin-Binding Site 1.

  Amarasinghe C, Jin JP. Amarasinghe C, et al. Biochemistry. 2015 Jun 23;54(24):3822-30. doi: 10.1021/acs.biochem.5b00348. Epub 2015 Jun 10. Biochemistry. 2015. PMID: 26024675

• Troponin T core structure and the regulatory NH2-terminal variable region.

  Biesiadecki BJ, Chong SM, Nosek TM, Jin JP. Biesiadecki BJ, et al. Biochemistry. 2007 Feb 6;46(5):1368-79. doi: 10.1021/bi061949m. Biochemistry. 2007. PMID: 17260966 Free PMC article.

• Selective deletion of the NH2-terminal variable region of cardiac troponin T in ischemia reperfusion by myofibril-associated mu-calpain cleavage.

  Zhang Z, Biesiadecki BJ, Jin JP. Zhang Z, et al. Biochemistry. 2006 Sep 26;45(38):11681-94. doi: 10.1021/bi060273s. Biochemistry. 2006. PMID: 16981728 Free PMC article.

• TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure-function relationships.

  Wei B, Jin JP. Wei B, et al. Gene. 2016 May 10;582(1):1-13. doi: 10.1016/j.gene.2016.01.006. Epub 2016 Jan 13. Gene. 2016. PMID: 26774798 Free PMC article. Review.

• Invertebrate troponin: Insights into the evolution and regulation of striated muscle contraction.

  Cao T, Thongam U, Jin JP. Cao T, et al. Arch Biochem Biophys. 2019 May 15;666:40-45. doi: 10.1016/j.abb.2019.03.013. Epub 2019 Mar 27. Arch Biochem Biophys. 2019. PMID: 30928296 Free PMC article. Review.

Cited by

• Metabolic Pathway of Cardiospecific Troponins: From Fundamental Aspects to Diagnostic Role (Comprehensive Review).

  Chaulin AM. Chaulin AM. Front Mol Biosci. 2022 Apr 19;9:841277. doi: 10.3389/fmolb.2022.841277. eCollection 2022. Front Mol Biosci. 2022. PMID: 35517866 Free PMC article. Review.

• Doxorubicin-Induced Cardiotoxicity: An Overview on Pre-clinical Therapeutic Approaches.

  Sheibani M, Azizi Y, Shayan M, Nezamoleslami S, Eslami F, Farjoo MH, Dehpour AR. Sheibani M, et al. Cardiovasc Toxicol. 2022 Apr;22(4):292-310. doi: 10.1007/s12012-022-09721-1. Epub 2022 Jan 21. Cardiovasc Toxicol. 2022. PMID: 35061218 Review.

• Deep RNA sequencing of pectoralis muscle transcriptomes during late-term embryonic to neonatal development in indigenous Chinese duck breeds.

  Zhu C, Song W, Tao Z, Liu H, Xu W, Zhang S, Li H. Zhu C, et al. PLoS One. 2017 Aug 3;12(8):e0180403. doi: 10.1371/journal.pone.0180403. eCollection 2017. PLoS One. 2017. PMID: 28771592 Free PMC article.

• Structural and Functional Properties of Kappa Tropomyosin.

  Kopylova GV, Kochurova AM, Yampolskaya DS, Nefedova VV, Tsaturyan AK, Koubassova NA, Kleymenov SY, Levitsky DI, Bershitsky SY, Matyushenko AM, Shchepkin DV. Kopylova GV, et al. Int J Mol Sci. 2023 May 6;24(9):8340. doi: 10.3390/ijms24098340. Int J Mol Sci. 2023. PMID: 37176047 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • scite Smart Citations

• Miscellaneous

  • NCI CPTAC Assay Portal