Myosin light chain
A myosin light chain is a light chain (small polypeptide subunit) of myosin. Myosin light chains were discovered by Chinese biochemist Cao Tianqin (Tien-chin Tsao) when he was a graduate student at the University of Cambridge in England.
Structure and function
Myosin light chain classes
Structurally, myosin light chains belong to the EF-hand family, a large family of Ca2+- binding proteins. MLCs contain two Ca2+ - binding EF-hand motifs. MLCs isoforms modulate the Ca2+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 Ca2+-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.
- MYL1 (chromosome 2q24.11); expressed in striated muscle
- MYL3 (chromosome 3p21.3); expressed in striated muscle
- MYL4 (chromosome 17q21.32); expressed in striated muscle
- MYL6 (chromosome 12q13.2); expressed in non-muscle and smooth muscle
- MYL2 (chromosome 12q24.11); found in the sarcomere
- MYL5 (chromosome 4p16.3); found in the sarcomere
- MYL7 (chromosome 12q13.2); found in the sarcomere
- MYL9 (chromosome 20q11.23); expressed in smooth muscle
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 .
Interaction of MLCs with non-myosin proteins
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 .
- Myosin+Light+Chains at the US National Library of Medicine Medical Subject Headings (MeSH)
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- Kimura MY, Hayashizaki K, Tokoyoda K, Takamura S, Motohashi S, Nakayama T (July 2017). "Crucial role for CD69 in allergic inflammatory responses: CD69-Myl9 system in the pathogenesis of airway inflammation". Immunological Reviews. 278 (1): 87–100. doi:10.1111/imr.12559. PMID 28658550.
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