A myosin light chain is a light chain (small
polypeptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
subunit) 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 ...
. Myosin light chains were discovered by Chinese biochemist
Cao Tianqin
Cao Tianqin (; 5 December 1920 – 8 January 1995), also known as Tien-chin Tsao, was a Chinese biochemist and a professor at the Shanghai Institute of Biochemistry. With a research focus on muscle protein, he discovered the myosin light chain ...
(Tien-chin Tsao) when he was a graduate student at the
University of Cambridge
, mottoeng = Literal: From here, light and sacred draughts.
Non literal: From this place, we gain enlightenment and precious knowledge.
, established =
, other_name = The Chancellor, Masters and Schola ...
in England.
Structure and function
Myosin light chain classes
Structurally, myosin light chains belong to the EF-hand family, a large family of Ca
2+- binding proteins. MLCs contain two Ca
2+ - binding EF-hand motifs. MLCs isoforms modulate the Ca
2+of force transduction and cross-bridge kinetics.
Myosin light chains (MLCs) can be broadly classified into two groups:
* Essential or alkali MLC (MLC1 or ELC),
* Regulatory MLC (MLC2 or RLC).
Essential and regulatory MLCs have molecular masses of 22 and 19 kDa, respectively. Structurally, MLC2 contains a serine residue that is lacking in MLC1. The presence of this amino acids allows the regulation of the conformational changes (from compacted to an elongated form) by a Ca
2+-mediated phosphorylation mechanism. MLC1, in contrast with MLC2, has a N-terminal sequence able to bind actin, contributing to force production.
MLCs are structurally and functionally distinct from myosin heavy chains (MHCs). Nevertheless, the association of MLCs with the neck region of MHCs is necessary for the assembly of the macromolecular complexes that result in the functional motor protein, myosin. The interaction of MLCs with the α-helical neck region of MHC molecule stabilizes the complex .
Genes in mammalians
To this day, eight genes encoding for MLCs in mammalians have been described; several isoforms have also been characterized. Four out of the 8 genes are MLC1 genes, whilst the remaining are MLC2 genes.
MLC1 genes:
*''
MYL1
Myosin light chain 3, skeletal muscle isoform is a protein that in humans is encoded by the ''MYL1'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ...
'' ''(''chromosome 2q24.11); expressed in striated muscle
*''
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 ...
'' (chromosome 3p21.3); expressed in striated muscle
*''
MYL4
Atrial Light Chain-1 (ALC-1), also known as Essential Light Chain, Atrial is a protein that in humans is encoded by the ''MYL4'' gene. ALC-1 is expressed in fetal cardiac ventricular and fetal skeletal muscle, as well as fetal and adult cardiac ...
'' (chromosome 17q21.32); expressed in striated muscle
*''
MYL6
Myosin light polypeptide 6 is a protein that in humans is encoded by the ''MYL6'' gene.
Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatabl ...
'' (chromosome 12q13.2); expressed in non-muscle and smooth muscle
MLC2 genes:
*''
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 ...
'' (chromosome 12q24.11); found in the sarcomere
*''
MYL5'' (chromosome 4p16.3); found in the sarcomere
*''
MYL7
Atrial Light Chain-2 (ALC-2) also known as Myosin regulatory light chain 2, atrial isoform (MLC2a) is a protein that in humans is encoded by the ''MYL7'' gene. ALC-2 expression is restricted to cardiac muscle atria in healthy individuals, where it ...
'' (chromosome 12q13.2); found in the sarcomere
*''
MYL9
Myosin regulatory light polypeptide 9 is a protein that in humans is encoded by the ''MYL9'' gene.
Function
Myosin, a structural component of muscle, consists of two heavy chains and four light chains. The protein encoded by this gene is a myo ...
'' (chromosome 20q11.23); expressed in smooth muscle
Other proteins and enzymes related to MLC function have been described. Among them are, for example,
MYL6B
Myosin light chain 6B is a protein that in humans is encoded by the ''MYL6B'' gene. Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable r ...
,
MYLIP
Myosin regulatory light chain interacting protein, also known as MYLIP, is a protein that in humans is encoded by the ''MYLIP'' gene.
MYLIP is also known as IDOL "Inducible Degrader of the LDL receptor" based on its involvement in cholesterol reg ...
,
MYLK
Myosin light chain kinase, smooth muscle also known as kinase-related protein (KRP) or telokin is an enzyme that in humans is encoded by the ''MYLK'' gene.
Function
This gene, a muscle member of the immunoglobulin superfamily, encodes a myosin ...
, and
MYLK2
Myosin light chain kinase 2 also known as MYLK2 is an enzyme which in humans is encoded by the ''MYLK2'' gene.
Function
This gene encodes a myosin light chain kinase, a calcium / calmodulin dependent enzyme, that is exclusively expressed in ...
,
Diseases associated with MLCs
Several diseases have been associated with mutations in the genes encoding for myosin light chain proteins. The majority of these diseases are cardiomyopathies, such as hypertrophic (HCM) or dilated (DCM) cardiomyopathy and sudden cardiac death. Mutations in ''MYL2'' and ''MYL3'' have been reported for these diseases.
One study, published in 2012, found that valvular myosin 'LC1', in the hearts of three patients with valvular heart diseases, had structures similar to those of valvular myosin of people who were in their early stages of DCMP and HCMP. The researchers hypothesized that the structure distortion of these valvular myosin were due to adaptational changes by the body in an attempt to improve the functioning of the heart.
MLCK's as Biological Drugs
Myosin light chain kinase (MLCK) inhibitors are one of the few peptides that can cross the plasma membrane relatively quickly. Under stressful conditions, MLCK's in the human body promotes increased permeability of microvessels. It is thought that MLCK phosphorylates endothelial myosin, leading to cell contraction. This reaction prevents disengaged cells that are adjacent to one another from reestablishing connections, thus contributing to the maintenance of the gaps between cells. With their strong ability to cross the plasma membrane with little resistance from the cell, along with their specificity for a single target-substrate, MLCK inhibitors can potentially evolve into novel
antiedemic drugs.
Interaction of MLCs with non-myosin proteins
''
MYL9
Myosin regulatory light polypeptide 9 is a protein that in humans is encoded by the ''MYL9'' gene.
Function
Myosin, a structural component of muscle, consists of two heavy chains and four light chains. The protein encoded by this gene is a myo ...
'', ''MYL12a,'' and ''
MYL12b Myosin, light chain 12B, regulatory is a protein that in humans is encoded by the ''MYL12B'' gene. The gene is also known as ''MLC-B'' and ''MRLC2''. The activity of nonmuscle myosin II is regulated by phosphorylation of a regulatory light chain, s ...
(MYL9/12)'' have been described as new functional interaction partners with
CD69
CD69 (Cluster of Differentiation 69) is a human transmembrane C-Type lectin protein encoded by the gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is ...
in the pathogenesis of inflammation of the airways.
A novel mechanism of activated T cell recruitment into inflammatory tissues has been proposed, known was "CD69/Myl9/12 system". The proposed mechanism state that "Myl9/12-containing net-like structures are created in inflammatory vessels, which play an important role as a platform for recruitment of CD69-expressing leukocytes into inflammatory tissues. T cells that are activated in the lymph nodes proliferate, down-regulate CD69 expression, and then leave the lymph nodes to migrate into inflammatory sites in an S1PR1-dependent manner."
The proposed mechanisms of action of CD69/Myl9/12 system are related to the regulation of airway inflammatory processes and thus can prove to be a novel therapeutic target for chronic inflammatory diseases, in general.
See also
*
Myosin light-chain kinase
Myosin light-chain kinase also known as MYLK or MLCK is a serine/threonine-specific protein kinase that phosphorylates a specific myosin light chain, namely, the regulatory light chain of myosin II.
General structural features
While there ar ...
*
Myosin-light-chain phosphatase
Myosin light-chain phosphatase, also called myosin phosphatase (EC 3.1.3.53; systematic name yosin-light-chainphosphate phosphohydrolase), is an enzyme (specifically a Protein serine/threonine phosphatase, serine/threonine-specific protein pho ...
References
{{Cytoskeletal Proteins
Motor proteins