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spinqualitylabelsall models PDB ID 2mys Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2mys, resolution 2.80Å ()
Ligands:	,
Non-Standard Residues:
Structural annotation: Resources: InterPro : Ipr001609, Ipr015650, Ipr002928, Ipr000048, Ipr004009 Pfam : PF00063, PF02736, PF00612 SCOP : d2mysa2, d2mysa1 UniProt : P13538, P02609, P02604
Functional annotation: Cellular component: myosin complex striated muscle thick filament Biological process: striated muscle contraction Molecular function: ATP binding actin binding calmodulin binding motor activity nucleotide binding
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Proteolytic fragment of myosin generated by papain digestion in Gallus gallus (chicken) bound to ligands and

Structure

Myosin is a 520 kDa hexamer, or a hexa-oligomer (6 subunit) structure. It is comprised of two heavy chains (weighing 220 kDa each) and 4 light chains (weighing 20 kDa each).^[3]

Secondary Structure

The N-terminal comprises a globular head in the heavy chains, and the C-terminal ends with an alpha helix. The globular head region is also known as S1 (actin-binding site and nucleotide-binding site), and also contains mostly alpha-helices that are critical to maintaining structure. The C-terminal end contains interspersed hydrophobic regions that give rise to a "coiled coil" structure.^[3]

Active Site

The actin-binding, of myosin is known as S1 (subfragment 1). This is the amino-terminal globular head portion of the myosin molecule. The S1 head is divided into three subdomains: the NH2-terminal 25 kDa region, a central 50 kDa region, and the COOH-terminal 20 kDa region. Further analysis of the S1 active site of myosin suggests that the γ-phosphate (of ATP) binds near the apex of the 50 kDa cleft. It is believed to be a region critical to function, because of the presence of evolutionarily conserved residues along the central cleft.^[2] The actin-binding site and nucleotide-binding site, although dominated by alpha-helices, also contains a straightened section with two cysteine residues. The can form a disulfide bond in the presence of a nucleotide that prevents ADP from leaving the active site.^[3]

X-Ray Crystallography and Diffraction

It was not until recently that crystal structures could be used to analyze myosin and it's role in the actinomysin chemomechanical cycle. X-ray diffraction studies have been conducted on whole muscles and muscle fibers to learn how structural changes promote and facilitate motor activity. Movement of myosin was analyzed under near physiological conditions using modern synchrotron radiation sources. Structural alterations were created through use of unique time and spatial resolution. Muscle cells exhibit low scattering power in X-ray images, so a clear crystalline structure cannot not form. A flat detector is needed because reflections are concentrated in the low angle regions. Snychrotron radiation generates a monochromatic X-ray breams of diameter 0.2-0.3 mm, similar to that of the muscle fiber, and making high resolution images and video of a single muscle cell possible.^[4]

Mechanism of Action

Myosin plays a role in the universal mechanism known as the actinomysin chemomechanical cycle. Actin binds and releases myosin, causing the myosin lever to interact and relax in a cyclic manner.^[1]

1. ATP binds to S1 causing Actin to disassociate out of it's rigor complex (between actin and the S1 catalytic site on myosin)
2. S1 causes the hydolysis of ATP to ADP and Pi
3. Actin interacts with the S1-ADP-Pi complex and Pi is released
4. S1 catalytic site's affinity for actin increases and the Actin-S1-ADP forms
5. ADP is released, causing actin and myosin to again enter into the tightly bound rigor complex^[2][4]

Medical Implications and Possible Applications

The discovery of myosin structure served as a crucial component in understanding the causes of many health related problems. Dysfunctional myosin mutations have been linked to hypertrophy in the heart. The heart enlarges to compensate for inadequate cardiac muscle contractions and consequent poor blood circulation. Also, blood platelet contractile protein aggregation and secretion is impeded by faulty myosin in patients suffering from idiopathic scoliosis. A defect in the less-well known myosin VIIA causes Usher 1B syndrome; causing a loss of sight and hearing impairments. Further research will hopefully give more insight into the unknown causes of other diseases and disorders linked to myosin protein mutations.^[3]

References

1. ↑ ^{1.0 1.1} Varkuti BH, Yang Z, Kintses B, Erdelyi P, Bardos-Nagy I, Kovacs AL, Hari P, Kellermayer M, Vellai T, Malnasi-Csizmadia A. A novel actin binding site of myosin required for effective muscle contraction. Nat Struct Mol Biol. 2012 Feb 12;19(3):299-306. doi: 10.1038/nsmb.2216. PMID:22343723 doi:10.1038/nsmb.2216
2. ↑ ^{2.0 2.1 2.2} Ruppel KM, Spudich JA. Structure-function studies of the myosin motor domain: importance of the 50-kDa cleft. Mol Biol Cell. 1996 Jul;7(7):1123-36. PMID:8862525
3. ↑ ^{3.0 3.1 3.2 3.3} [1]
4. ↑ ^{4.0 4.1} Koubassova NA, Tsaturyan AK. Molecular mechanism of actin-myosin motor in muscle. Biochemistry (Mosc). 2011 Dec;76(13):1484-506. doi: 10.1134/S0006297911130086. PMID:22339600 doi:10.1134/S0006297911130086