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| | ==Myosin VI motor domain in the Pre-Transition State== | | ==Myosin VI motor domain in the Pre-Transition State== |
| - | <StructureSection load='5o2l' size='340' side='right' caption='[[5o2l]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='5o2l' size='340' side='right'caption='[[5o2l]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5o2l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O2L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O2L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5o2l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O2L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O2L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYO6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5o2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o2l OCA], [http://pdbe.org/5o2l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o2l RCSB], [http://www.ebi.ac.uk/pdbsum/5o2l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o2l ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5o2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o2l OCA], [https://pdbe.org/5o2l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o2l RCSB], [https://www.ebi.ac.uk/pdbsum/5o2l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o2l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MYO6_PIG MYO6_PIG] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells (By similarity).<ref>PMID:16917816</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5o2l" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5o2l" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Myosin 3D Structures|Myosin 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pig]] | + | [[Category: Large Structures]] |
| - | [[Category: Benisty, H]] | + | [[Category: Sus scrofa]] |
| - | [[Category: Houdusse, A]] | + | [[Category: Benisty H]] |
| - | [[Category: Isabet, T]] | + | [[Category: Houdusse A]] |
| - | [[Category: Motor domain]] | + | [[Category: Isabet T]] |
| - | [[Category: Motor protein]]
| + | |
| - | [[Category: Myosin]]
| + | |
| - | [[Category: Pre-transition state]]
| + | |
| Structural highlights
Function
MYO6_PIG Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells (By similarity).[1]
Publication Abstract from PubMed
Myosins form a class of actin-based, ATPase motor proteins that mediate important cellular functions such as cargo transport and cell motility. Their functional cycle involves two large-scale swings of the lever arm: the force-generating powerstroke, which takes place on actin, and the recovery stroke during which the lever arm is reprimed into an armed configuration. Previous analyses of the prerecovery (postrigor) and postrecovery (prepowerstroke) states predicted that closure of switch II in the ATP binding site precedes the movement of the converter and the lever arm. Here, we report on a crystal structure of myosin VI, called pretransition state (PTS), which was solved at 2.2 A resolution. Structural analysis and all-atom molecular dynamics simulations are consistent with PTS being an intermediate along the recovery stroke, where the Relay/SH1 elements adopt a postrecovery conformation, and switch II remains open. In this state, the converter appears to be largely uncoupled from the motor domain and explores an ensemble of partially reprimed configurations through extensive, reversible fluctuations. Moreover, we found that the free energy cost of hydrogen-bonding switch II to ATP is lowered by more than 10 kcal/mol compared with the prerecovery state. These results support the conclusion that closing of switch II does not initiate the recovery stroke transition in myosin VI. Rather, they suggest a mechanism in which lever arm repriming would be mostly driven by thermal fluctuations and eventually stabilized by the switch II interaction with the nucleotide in a ratchet-like fashion.
An intermediate along the recovery stroke of myosin VI revealed by X-ray crystallography and molecular dynamics.,Blanc F, Isabet T, Benisty H, Sweeney HL, Cecchini M, Houdusse A Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):6213-6218. doi:, 10.1073/pnas.1711512115. Epub 2018 May 29. PMID:29844196[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Naccache SN, Hasson T. Myosin VI altered at threonine 406 stabilizes actin filaments in vivo. Cell Motil Cytoskeleton. 2006 Oct;63(10):633-45. PMID:16917816 doi:http://dx.doi.org/10.1002/cm.20150
- ↑ Blanc F, Isabet T, Benisty H, Sweeney HL, Cecchini M, Houdusse A. An intermediate along the recovery stroke of myosin VI revealed by X-ray crystallography and molecular dynamics. Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):6213-6218. doi:, 10.1073/pnas.1711512115. Epub 2018 May 29. PMID:29844196 doi:http://dx.doi.org/10.1073/pnas.1711512115
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