β-Tropomyosin, also known as tropomyosin beta chain is a
protein that in humans is encoded by the TPM2gene.[5][6] β-tropomyosin is striated muscle-specific
coiled coil dimer that functions to stabilize
actin filaments and regulate
muscle contraction.
Structure
β-tropomyosin is roughly 32 kDa in molecular weight (284 amino acids), but multiple splice variants exist.[7][8][9][10] Tropomysin 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. It is polymerized end to end along the two grooves of
actin filaments and provides stability to the filaments.[11] Tropomyosin dimers are composed of varying combinations of tropomyosin isoforms; human
striated muscles express protein from the TPM1 (α-tropoomyosin), TPM2 (β-tropomyosin) and TPM3 (γ-tropomyosin) genes, with
α-tropomyosin being the predominant isoform in striated muscle. Fast
skeletal muscle and
cardiac muscle contain more αα-homodimers, and slow
skeletal muscle contains more ββ-homodimers.[12] In human
cardiac muscle the ratio of
α-tropomyosin to β-tropomyosin is roughly 5:1.[13][14] It has been shown that different combinations of tropomyosin isoforms bind
troponin T with differing affinities, demonstrating that isoform combinations are used to impart a specific functional impact.[12]
Specific functional insights into the function of the β-tropomyosin
isoform have come from studies employing transgenesis. A study overexpressing β-tropomyosin in adult
cardiac muscle evoked a 34-fold increase in expression of β-tropomyosin, resulting in preferential formation of the αβ-tropomyosin heterodimer. Transgenic hearts showed a significant delay in
relaxation time as well as a decrease in the maximum rate of left
ventricularrelaxation.[12] A more aggressive overexpression of β-tropomyosin (to over 75% of total tropomyosin) in the heart causes death of mice 10–14 days old, along with cardiac abnormalities, suggesting that the normal distribution of tropomyosin isoforms is critical to normal cardiac function.[15]
In a disease model of
cardiac hypertrophy, β-tropomyosin was shown to be reexpressed within two days following induction of pressure overload.[16]
Studies from mice, which express 98%
α-tropomyosin, have shown that α-tropomyosin can be
phosphorylated at
Serine-283, which is one
amino acid away from the
C-terminus. β-tropomyosin also has a
Serine residue at position 283,[17] thus, it is likely that β-tropomyosin is also
phosphorylated. Mouse transgenic studies in which the
phosphorylation site in
α-tropomyosin is mutated to
Alanine have shown that
phosphorylation may function to modulate tropomyosin polymerization, head-to-tail interactions between adjacent tropomyosin molecules, cooperativity,
myosinATPase activity, and the cardiac response to stress.[18]
Heterozygous mutations in TPM2 have been identified in patients with congenital cap myopathy, a rare disorder defined by cap-like structures in muscle fiber periphery.[20][21][22][23]
Mutations in TPM2 have also been associated with
nemaline myopathy, a rare disorder characterized by muscle weakness and nemaline bodies,[24][25][26]
The muscle weakness observed in these patients may be due to a change in mutated TPM2 affinity for
actin or decreased
calcium-induced activation of
contractility.[29][30][31] Moreover, studies unveiled alterations in cross-bridge attachment and detachment rates,[32] as well as changes in ATPase rates.[30][33]
^Muthuchamy M, Boivin GP, Grupp IL, Wieczorek DF (Aug 1998). "Beta-tropomyosin overexpression induces severe cardiac abnormalities". Journal of Molecular and Cellular Cardiology. 30 (8): 1545–57.
doi:
10.1006/jmcc.1998.0720.
PMID9737941.
^Schulz, EM; Wieczorek, DF (August 2013). "Tropomyosin de-phosphorylation in the heart: what are the consequences?". Journal of Muscle Research and Cell Motility. 34 (3–4): 239–46.
doi:
10.1007/s10974-013-9348-7.
PMID23793376.
S2CID15297144.
^Ohlsson M, Quijano-Roy S, Darin N, Brochier G, Lacène E, Avila-Smirnow D, Fardeau M, Oldfors A, Tajsharghi H (Dec 2008). "New morphologic and genetic findings in cap disease associated with beta-tropomyosin (TPM2) mutations". Neurology. 71 (23): 1896–901.
doi:
10.1212/01.wnl.0000336654.44814.b8.
PMID19047562.
S2CID24356825.
^Lehtokari VL, Ceuterick-de Groote C, de Jonghe P, Marttila M, Laing NG, Pelin K, Wallgren-Pettersson C (Jun 2007). "Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2". Neuromuscular Disorders. 17 (6): 433–42.
doi:
10.1016/j.nmd.2007.02.015.
PMID17434307.
S2CID54349245.
^Clarke NF, Domazetovska A, Waddell L, Kornberg A, McLean C, North KN (May 2009). "Cap disease due to mutation of the beta-tropomyosin gene (TPM2)". Neuromuscular Disorders. 19 (5): 348–51.
doi:
10.1016/j.nmd.2009.03.003.
PMID19345583.
S2CID38636941.
^Donner K, Ollikainen M, Ridanpää M, Christen HJ, Goebel HH, de Visser M, Pelin K, Wallgren-Pettersson C (Feb 2002). "Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy". Neuromuscular Disorders. 12 (2): 151–8.
doi:
10.1016/s0960-8966(01)00252-8.
PMID11738357.
S2CID54360043.
^Tajsharghi H, Kimber E, Holmgren D, Tulinius M, Oldfors A (Mar 2007). "Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation". Neurology. 68 (10): 772–5.
doi:
10.1212/01.wnl.0000256339.40667.fb.
PMID17339586.
S2CID41982388.
Höner B, Shoeman RL, Traub P (Jul 1992). "Degradation of cytoskeletal proteins by the human immunodeficiency virus type 1 protease". Cell Biology International Reports. 16 (7): 603–12.
doi:
10.1016/S0309-1651(06)80002-0 (inactive 2024-03-27).
PMID1516138.{{
cite journal}}: CS1 maint: DOI inactive as of March 2024 (
link)
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Tiso N, Rampoldi L, Pallavicini A, Zimbello R, Pandolfo D, Valle G, Lanfranchi G, Danieli GA (Jan 1997). "Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta-tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast". Biochemical and Biophysical Research Communications. 230 (2): 347–50.
doi:
10.1006/bbrc.1996.5958.
PMID9016781.
Gimona M, Lando Z, Dolginov Y, Vandekerckhove J, Kobayashi R, Sobieszek A, Helfman DM (Mar 1997). "Ca2+-dependent interaction of S100A2 with muscle and nonmuscle tropomyosins". Journal of Cell Science. 110 (5): 611–21.
doi:
10.1242/jcs.110.5.611.
PMID9092943.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56.
doi:
10.1016/S0378-1119(97)00411-3.
PMID9373149.