MYH7 is a
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 ba ...
encoding a
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 ...
heavy chain beta (MHC-β) isoform (slow twitch) expressed primarily in the heart, but also in skeletal muscles (type I fibers). This isoform is distinct from the fast isoform of cardiac myosin heavy chain,
MYH6
Myosin heavy chain, α isoform (MHC-α) is a protein that in humans is encoded by the ''MYH6'' gene. This isoform is distinct from the ventricular/slow myosin heavy chain isoform, MYH7, referred to as MHC-β. MHC-α isoform is expressed predominant ...
, referred to as MHC-α. MHC-β is the major protein comprising the thick filament in cardiac muscle and plays a major role in 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
MHC-β is a 223 kDa protein composed of 1935 amino acids. MHC-β is a hexameric, asymmetric motor forming the bulk of the thick filament in cardiac muscle. MHC-β is composed of N-terminal globular heads (20 nm) that project laterally, and alpha helical tails (130 nm) that dimerize and multimerize into a coiled-coil motif to form the light meromyosin (LMM), thick filament rod. The 9 nm alpha-helical neck region of each MHC-β head non-covalently binds two light chains, essential light chain (
MYL3
Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the ''MYL3'' gene. This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (MYL1) and card ...
) and regulatory light chain (
MYL2
Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin (RLC) is a protein that in humans is encoded by the ''MYL2'' gene. This cardiac ventricular RLC isoform is distinct from ...
). Approximately 300 myosin molecules constitute one thick filament. There are two isoforms of cardiac MHC, α and β, which display 93% homology. MHC-α and MHC-β display significantly different enzymatic properties, with α having 150-300% the contractile velocity and 60-70% actin attachment time as that of β. MHC-β is predominately expressed in the human ventricle, while MHC-α is predominantly expressed in human atria.
Function
It is the enzymatic activity of the ATPase in the myosin head that cyclically hydrolyzes ATP, fueling the myosin power stroke. This process converts chemical to mechanical energy, and propels shortening of the sarcomeres in order to generate intraventricular pressure and power. An accepted mechanism for this process is that ADP-bound myosin attaches to actin while thrusting tropomyosin inwards, then the S1-S2 myosin lever arm rotates ~70° about the converter domain and drives actin filaments towards the M-line.
Clinical significance
Several mutations in MYH7 have been associated with inherited cardiomyopathies. Lowrance et al. were the first to identify the causative mutation
Arg403
Gln for
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 ...
(HCM) in the MYH7 gene. Studies have since identified several more MYH7 mutations, that are estimated to be causal in approximately 40% of
HCM cases. This condition is an
autosomal-dominant disease
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
, in which a single copy of the variant gene causes enlargement of the left
ventricle of the heart. Disease onset usually occurs later in life, perhaps triggered by changes in
thyroid hormone
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
function and/or physical stress.
Another condition associated to mutations in this gene is paraspinal and proximal muscle atrophy.
References
Further reading
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External links
Mass spectrometry characterization of MYH7 at COPaKB *
{{Cytoskeletal Proteins
Motor proteins
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