MYL3

Myosin essential light chain (ELC), ventricular/cardiac isoform is a is_associated_with::protein that in humans is encoded by the MYL3 is_associated_with::gene. This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (is_associated_with::MYL1) and cardiac atrial muscle (is_associated_with::MYL4). Ventricular ELC is part of the myosin molecule and is important in modulating cardiac is_associated_with::muscle contraction.

Structure
Cardiac, ventricular ELC is 21.9 kDa and composed of 195 amino acids (See human MYL3 sequences features here). Cardiac ELC and the second light chain, regulatory light chain (RLC, is_associated_with::MYL2), are non-covalently bound to IQXXXRGXXXR motifs in the 9 nm S1-S2 lever arm of the myosin head, both alpha (is_associated_with::MYH6) and beta (is_associated_with::MYH7) isoforms. Both light chains are members of the is_associated_with::EF-hand superfamily of proteins, which possess helix-loop-helix motifs in two globular domains connected by an alpha-helical linker. Though EF hand motifs are specialized to bind divalent ions such as calcium, cardiac ELC does not bind calcium at physiological levels. The N-terminal region of cardiac ELC is functionlly unique in that it is positively charged, being rich in is_associated_with::Lysine residues (amino acids 4-14), with subsequent unique structure governed by is_associated_with::Proline-is_associated_with::Alanine repeats (amino acids 15-36).

Function
Studies have provided evidence for ELC as modulator of myosin crossbrige kinetics. Treating cardiac myofibrils with the is_associated_with::Lysine-rich N-terminal peptide (amino acids 5-14) evoked a supramaximal increase in cardiac myofibrillar MgATPase activity at submaximal calcium concentrations, and further studies demonstrated that this region of ELC modulates the affinity of is_associated_with::myosin for is_associated_with::actin.

Clinical significance
Mutations in MYL3 have been identified as a cause of familial is_associated_with::hypertrophic cardiomyopathy, and associated with a mid-left ventricular chamber type hypertrophy. Five mutations in MYL3 have been identified to date: M149V, R154H, E56G, A57G and E143K. All of these cluster around two of the four is_associated_with::EF-hand domains, suggesting that proper conformation in these regions is necessary for normal cardiac function.