Sandbox Reserved 479

This Sandbox is Reserved from 13/03/2012, through 01/06/2012 for use in the course "Proteins and Molecular Mechanisms" taught by Robert B. Rose at the North Carolina State University, Raleigh, NC USA. This reservation includes Sandbox Reserved 451 through Sandbox Reserved 500.

To get started: Click the edit this page tab at the top. Save the page after each step, then edit it again. Click the 3D button (when editing, above the wikitext box) to insert Jmol. show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page. Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc. More help: Help:Editing For more help, look at this link: http://www.proteopedia.org/wiki/index.php/Help:Getting_Started_in_Proteopedia MYOSINMYOSIN Myosin is comprised of many different classes of motor proteins within one of three families: actin-based myosin, microtubule-based kinesin, and dynein. There are 35 classes of myosin within the actin-based myosin family of motor proteins, and they are universal in all eukaryotic cells. Myosin II is the more well known form of myosin that is involved in muscle contractions; it acts in complex with actin to create a powerstroke and cause muscular contraction and relaxation. Myosin is the contractile unit of a sarcomere. Repeating units of sarcomeres make up a myofibril (muscle fiber), and bundles of fibers make up a skeletal muscle. The figure below (right) is a proteolytic fragment of myosin generated by papain digestion in Gallus gallus (chicken). 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 StructureStructure 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). The hexamer's 2 identical heavy chains connected via the coiled coil structure, and each containing a regulatory and essential light chain (total of 4). The 2-D structure below of myosin II head shows 7 stranded (Jmol) and the ATP-binding site between the middle and N-terminal of the protein. The C-terminal contains the light chains (regulatory domain) and acts as the lever arm to enhance the converter domain's rotational movements. Secondary StructureSecondary 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 that are critical to maintaining structure. The C-terminal end contains interspersed hydrophobic regions that give rise to a "coiled-coil structure. Active SiteActive Site The actin-binding, of myosin is known as S1 (subfragment 1). This is the amino-terminal (N-terminal) globular head portion of the myosin molecule in a region known as the activation loop. 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. 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. X-Ray Crystallography and ScatteringX-Ray Crystallography and Scattering 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. Modern synchrotron radiation sources allow us to study myosin at the molecular level under near-physiological conditions. Muscle cells exhibit low scattering power in X-ray images, however, 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 via x-ray scattering patterns. New technology using snychrotron radiation and 2 dimensional detectors will allow researchers to gain even more insight into the structure of myosin and it's interaction with actin in unique time and spatial resolution. Interaction with ActinInteraction with Actin Myosin disassociates and binds to actin via the hydrolysis of ATP into ADP and Pi. The force behind a muscle contraction is due to the swinging lever arm (myosin). Mechanism of ActionMechanism 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. Actin and myosin cross bridge enter into the tightly bound rigor complex Working stroke occurs where myosin head pulls actin ATP attaches to myosin head causing it to detach from actin ATP is hydrolyzed into ADP and Pi. Myosin head prepares for attachment to actin filament again Medical Implications and Possible ApplicationsMedical 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 power strokes are weaker, making muscle contractions less effective. 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. ReferencesReferences