TPM1

Tm is a 32.7 kDa protein composed of 284 amino acids.{{cite web |title=Protein Information |url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P09493 |access-date=25 May 2023 |archive-url=https://web.archive.org/web/20150924025508/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P09493 |archive-date=September 24, 2015 |language=en |url-status=unfit | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) }} 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.{{cite journal | vauthors = Brown JH, Kim KH, Jun G, Greenfield NJ, Dominguez R, Volkmann N, Hitchcock-DeGregori SE, Cohen C | title = Deciphering the design of the tropomyosin molecule | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 15 | pages = 8496–8501 | date = July 2001 | pmid = 11438684 | pmc = 37464 | doi = 10.1073/pnas.131219198 | doi-access = free | bibcode = 2001PNAS...98.8496B }} 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.{{cite journal | vauthors = Yin Z, Ren J, Guo W | title = Sarcomeric protein isoform transitions in cardiac muscle: a journey to heart failure | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1852 | issue = 1 | pages = 47–52 | date = January 2015 | pmid = 25446994 | pmc = 4268308 | doi = 10.1016/j.bbadis.2014.11.003 }}

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,{{cite journal | vauthors = McKillop DF, Geeves MA | title = Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament | journal = Biophysical Journal | volume = 65 | issue = 2 | pages = 693–701 | date = August 1993 | pmid = 8218897 | pmc = 1225772 | doi = 10.1016/S0006-3495(93)81110-X | bibcode = 1993BpJ....65..693M }} 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.

Mutations in TPM1 have been associated with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy (LVNC). HCM mutations tend to cluster around the N-terminal region and a primary actin binding region known as period 5.{{cite journal | vauthors = Tardiff JC | title = Thin filament mutations: developing an integrative approach to a complex disorder | journal = Circulation Research | volume = 108 | issue = 6 | pages = 765–782 | date = March 2011 | pmid = 21415410 | pmc = 3075069 | doi = 10.1161/CIRCRESAHA.110.224170 }}

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• {{cite journal | vauthors = Cho YJ, Liu J, Hitchcock-DeGregori SE | title = The amino terminus of muscle tropomyosin is a major determinant for function | journal = The Journal of Biological Chemistry | volume = 265 | issue = 1 | pages = 538–545 | date = January 1990 | pmid = 2136742 | doi = 10.1016/S0021-9258(19)40264-0 | doi-access = free }}
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{{PDB Gallery|geneid=7168}}

• [http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P09493 Mass spectrometry characterization of human TPM1 at COPaKB] {{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–1053 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}
• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hyper-card GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview]
• {{PDBe-KB2|P09493|Tropomyosin alpha-1 chain}}

{{Cytoskeletal Proteins}}