Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1gene.[5] This gene is a member of the tropomyosin (Tm) family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells.
Structure
Tm is a 32.7 kDa protein composed of 284 amino acids.[6] Tm is a flexible protein homodimer or heterodimer composed of two alpha-helical chains, which adopt a bent coiled coil conformation to wrap around the seven actin molecules in a functional unit of muscle.[7] It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. Human striated muscles express protein from the TPM1 (α-Tm), TPM2 (β-Tm) and TPM3 (γ-Tm) genes, with α-Tm being the predominant isoform in striated muscle. In human cardiac muscle the ratio of α-Tm to β-Tm is roughly 5:1.[8]
Function
Tm functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. Tm molecules are arranged head-to-tail along the actin thin filament, and are a key component in cooperative activation of muscle. A three state model has been proposed by McKillop and Geeves,[9] which describes the positions of Tm during a cardiac cycle. The blocked (B) state occurs in diastole when intracellular calcium is low and Tm blocks the myosin binding site on actin. The closed (C) state is when Tm is positioned on the inner groove of actin; in this state myosin is in a "cocked" position where heads are weakly bound and not generating force. The myosin binding (M) state is when Tm is further displaced from actin by myosin crossbridges that are strongly-bound and actively generating force. In addition to actin, Tm binds troponin T (TnT). TnT tethers the region of head-to-tail overlap of subsequent Tm molecules to actin.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Mogensen J, Kruse TA, Børglum AD (Jun 1999). "Refined localization of the human alpha-tropomyosin gene (TPM1) by genetic mapping". Cytogenetics and Cell Genetics. 84 (1–2): 35–36. doi:10.1159/000015207. PMID10343096. S2CID84901339.
^"Protein Information". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on September 24, 2015. Retrieved 25 May 2023.{{cite web}}: CS1 maint: unfit URL (link)
Balvay L, Fiszman MY (1995). "[Analysis of the diversity of tropomyosin isoforms]". Comptes Rendus des Séances de la Société de Biologie et de ses Filiales. 188 (5–6): 527–540. PMID7780795.
Gunning P, Weinberger R, Jeffrey P (April 1997). "Actin and tropomyosin isoforms in morphogenesis". Anatomy and Embryology. 195 (4): 311–315. doi:10.1007/s004290050050. PMID9108196. S2CID9692297.
Höner B, Shoeman RL, Traub P (July 1992). "Degradation of cytoskeletal proteins by the human immunodeficiency virus type 1 protease". Cell Biology International Reports. 16 (7): 603–612. doi:10.1016/S0309-1651(06)80002-0 (inactive 2024-11-04). PMID1516138.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
Mische SM, Manjula BN, Fischetti VA (February 1987). "Relation of streptococcal M protein with human and rabbit tropomyosin: the complete amino acid sequence of human cardiac alpha tropomyosin, a highly conserved contractile protein". Biochemical and Biophysical Research Communications. 142 (3): 813–818. doi:10.1016/0006-291X(87)91486-0. PMID3548719.
Tanokura M, Ohtsuki I (May 1984). "Interactions among chymotryptic troponin T subfragments, tropomyosin, troponin I and troponin C". Journal of Biochemistry. 95 (5): 1417–1421. doi:10.1093/oxfordjournals.jbchem.a134749. PMID6746613.
