TPM2

β-Tropomyosin, also known as tropomyosin beta chain is a is_associated_with::protein that in humans is encoded by the TPM2 is_associated_with::gene. β-tropomyosin is striated muscle-specific is_associated_with::coiled coil dimer that functions to stabilize actin filaments and regulate is_associated_with::muscle contraction.

Structure
β-tropomyosin is roughly 32 kDa in molecular weight (284 amino acids), but multiple splice variants exist. Tropomysin is a flexible protein homodimer or heterodimer composed of two alpha-helical chains, which adopt a bent is_associated_with::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. Tropomyosin dimers are composed of varying combinations of tropomyosin isoforms; human is_associated_with::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 is_associated_with::skeletal muscle and is_associated_with::cardiac muscle contain more αα-homodimers, and slow is_associated_with::skeletal muscle contains more ββ-homodimers. In human is_associated_with::cardiac muscle the ratio of α-tropomyosin to β-tropomyosin is roughly 5:1. 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.

Function
β-tropomyosin functions in association with α-tropomyosin and the is_associated_with::troponin complex--composed of troponin I, troponin C and troponin T--to modulated the actin and myosin interaction. In is_associated_with::diastole, the tropomyosin-is_associated_with::troponin complex inhibits this interaction, and during is_associated_with::systole the rise in intracellular is_associated_with::calcium from is_associated_with::sarcoplasmic reticulum binds to troponin C and induces a conformational change in the is_associated_with::troponin-tropomyosin complex that disinhibits the actomyosin ATPase and permits is_associated_with::contraction.

Specific functional insights into the function of the β-tropomyosin is_associated_with::isoform have come from studies employing transgenesis. A study overexpressing β-tropomyosin in adult is_associated_with::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 ventricular relaxation. 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.

In a disease model of is_associated_with::cardiac hypertrophy, β-tropomyosin was shown to be reexpressed within two day following induction of pressure overload.

Studies from mice, which express 98% α-tropomyosin, have shown that α-tropomyosin can be phosphorylated at is_associated_with::Serine-283, which is one is_associated_with::amino acid away from the is_associated_with::C-terminus. β-tropomyosin also has a is_associated_with::Serine residue at position 283, thus, it is likely that β-tropomyosin is also phosphorylated. Mouse transgenic studies in which the is_associated_with::phosphorylation site in α-tropomyosin is mutated to is_associated_with::Alanine have shown that is_associated_with::phosphorylation may function to modulate tropomyosin polymerization, head-to-tail interactions between adjacent tropomyosin molecules, cooperativity, is_associated_with::myosin is_associated_with::ATPase activity, and the cardiac response to stress.

Clinical significance
A decrease in β-tropomyosin in patients with is_associated_with::heart failure was demonstrated, as failing is_associated_with::ventricles expressed solely α-tropomyosin.

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.

Mutations in TPM2 have also been associated with is_associated_with::nemaline myopathy, a rare disorder characterized by muscle weakness and nemaline bodies,

as well as distal is_associated_with::arthrogryposis.

The muscle weakness observed in these patients may be due to a change in mutated TPM2 affinity for actin or decreased is_associated_with::calcium-induced activation of is_associated_with::contractility. Moreover, studies unveiled alterations in cross-bridge attachment and detachment rates, as well as changes in ATPase rates.

Interactions
TPM2 has been shown to interact with:
 * is_associated_with::RRAD,
 * is_associated_with::PDLIM7,
 * is_associated_with::TNNT3, and
 * is_associated_with::TPM1.