2bki: Difference between revisions

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[[Image:2bki.gif|left|200px]]<br /><applet load="2bki" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2bki, resolution 2.90&Aring;" />
'''MYOSIN VI NUCLEOTIDE-FREE (MDINSERT2-IQ) CRYSTAL STRUCTURE'''<br />


==Overview==
==Myosin VI nucleotide-free (MDinsert2-IQ) crystal structure==
Here we solve a 2.4-A structure of a truncated version of the, reverse-direction myosin motor, myosin VI, that contains the motor domain, and binding sites for two calmodulin molecules. The structure reveals only, minor differences in the motor domain from that in plus-end directed, myosins, with the exception of two unique inserts. The first is near the, nucleotide-binding pocket and alters the rates of nucleotide association, and dissociation. The second unique insert forms an integral part of the, myosin VI converter domain along with a calmodulin bound to a novel target, motif within the insert. This serves to redirect the effective 'lever arm', of myosin VI, which includes a second calmodulin bound to an 'IQ motif', towards the pointed (minus) end of the actin filament. This repositioning, largely accounts for the reverse directionality of this class of myosin, motors. We propose a model incorporating a kinesin-like uncoupling/docking, mechanism to provide a full explanation of the movements of myosin VI.
<StructureSection load='2bki' size='340' side='right'caption='[[2bki]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2bki]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BKI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2bki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bki OCA], [https://pdbe.org/2bki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bki RCSB], [https://www.ebi.ac.uk/pdbsum/2bki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bki ProSAT]</span></td></tr>
</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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bk/2bki_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bki ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Here we solve a 2.4-A structure of a truncated version of the reverse-direction myosin motor, myosin VI, that contains the motor domain and binding sites for two calmodulin molecules. The structure reveals only minor differences in the motor domain from that in plus-end directed myosins, with the exception of two unique inserts. The first is near the nucleotide-binding pocket and alters the rates of nucleotide association and dissociation. The second unique insert forms an integral part of the myosin VI converter domain along with a calmodulin bound to a novel target motif within the insert. This serves to redirect the effective 'lever arm' of myosin VI, which includes a second calmodulin bound to an 'IQ motif', towards the pointed (minus) end of the actin filament. This repositioning largely accounts for the reverse directionality of this class of myosin motors. We propose a model incorporating a kinesin-like uncoupling/docking mechanism to provide a full explanation of the movements of myosin VI.


==About this Structure==
The structure of the myosin VI motor reveals the mechanism of directionality reversal.,Menetrey J, Bahloul A, Wells AL, Yengo CM, Morris CA, Sweeney HL, Houdusse A Nature. 2005 Jun 9;435(7043):779-85. PMID:15944696<ref>PMID:15944696</ref>
2BKI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with SO4 and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:So4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BKI OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
The structure of the myosin VI motor reveals the mechanism of directionality reversal., Menetrey J, Bahloul A, Wells AL, Yengo CM, Morris CA, Sweeney HL, Houdusse A, Nature. 2005 Jun 9;435(7043):779-85. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15944696 15944696]
</div>
<div class="pdbe-citations 2bki" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Calmodulin 3D structures|Calmodulin 3D structures]]
*[[Myosin 3D Structures|Myosin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
[[Category: Bahloul, A.]]
[[Category: Bahloul A]]
[[Category: Houdusse, A.]]
[[Category: Houdusse A]]
[[Category: Menetrey, J.]]
[[Category: Menetrey J]]
[[Category: Morris, C.]]
[[Category: Morris C]]
[[Category: Sweeney, H.L.]]
[[Category: Sweeney HL]]
[[Category: Wells, A.]]
[[Category: Wells A]]
[[Category: Yengo, C.]]
[[Category: Yengo C]]
[[Category: CA]]
[[Category: SO4]]
[[Category: calmodulin]]
[[Category: iq motif]]
[[Category: muscle protein]]
[[Category: myosin vi]]
[[Category: non-conventional myosin]]
[[Category: nucleotide-free conformation]]
[[Category: reverse myosin]]
 
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