Myosin essential light chain (ELC), ventricular/cardiac isoform is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''MYL3''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (
MYL1) and cardiac atrial muscle (
MYL4). Ventricular ELC is part of the
myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.
The first myosin (M ...
molecule and is important in modulating cardiac
muscle contraction
Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as ...
.
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,
MYL2), are non-covalently bound to IQXXXRGXXXR motifs in the 9 nm S1-S2 lever arm of the myosin head,
both alpha (
MYH6) and beta (
MYH7) isoforms. Both light chains are members of the
EF-hand
The EF hand is a helix–loop–helix structural domain or ''motif'' found in a large family of calcium-binding proteins.
The EF-hand motif contains a helix–loop–helix topology, much like the spread thumb and forefinger of the human hand, in ...
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 functionally unique in that it is positively charged, being rich in
Lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated &minu ...
residues (amino acids 4-14), with subsequent unique structure governed by
proline-
alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side ...
repeats (amino acids 15-36).
Function
Studies have provided evidence for ELC as modulator of myosin crossbridge kinetics. Treating cardiac myofibrils with the
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated &minu ...
-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
myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.
The first myosin (M ...
for
actin
Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...
.
Clinical significance
Mutations in MYL3 have been identified as a cause of familial
hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...
, 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
EF-hand
The EF hand is a helix–loop–helix structural domain or ''motif'' found in a large family of calcium-binding proteins.
The EF-hand motif contains a helix–loop–helix topology, much like the spread thumb and forefinger of the human hand, in ...
domains, suggesting that proper conformation in these regions is necessary for normal cardiac function.
References
Further reading
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External links
Mass spectrometry characterization of MYL3 at COPaKB GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview