View source for 4aqw


==Model of human kinesin-5 motor domain (1II6, 3HQD) and mammalian tubulin heterodimer (1JFF) docked into the 9.5-angstrom cryo-EM map of microtubule-bound kinesin-5 motor domain in the rigor state.==
<SX load='4aqw' size='340' side='right' viewer='molstar' caption='[[4aqw]], [[Resolution|resolution]] 9.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4aqw]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AQW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AQW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 9.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TA1:TAXOL'>TA1</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=4aqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aqw OCA], [https://pdbe.org/4aqw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aqw RCSB], [https://www.ebi.ac.uk/pdbsum/4aqw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aqw ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/TBA1D_BOVIN TBA1D_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
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== Publication Abstract from PubMed ==
Kinesin5 is required for forming the bipolar spindle during mitosis. Its motor domain, which contains nucleotide and microtubule binding sites and mechanical elements to generate force, has evolved distinct properties for its spindle based functions. In this study, we report subnanometer resolution cryoelectron microscopy reconstructions of microtubule bound human kinesin5 before and after nucleotide binding and combine this information with studies of the kinetics of nucleotide induced neck linker and cover strand movement. These studies reveal coupled, nucleotide dependent conformational changes that explain many of this motor's properties. We find that ATP binding induces a ratchet-like docking of the neck linker, and simultaneous, parallel docking of the amino-terminal cover strand. Loop L5-the binding site for allosteric inhibitors of kinesin5-also undergoes a dramatic reorientation when ATP binds, suggesting that it is directly involved in controlling nucleotide binding. Our structures indicate that allosteric inhibitors of human kinesin5, which are being developed as anti cancer therapeutics, bind to a motor conformation that occurs in the course of normal function. However, due to evolutionarily defined sequence variations in L5, this conformation is not adopted by invertebrate kinesin5s, explaining their resistance to drug inhibition. Together, our data reveal the precision with which the molecular mechanism of kinesin5 motors has evolved for force generation.

THE STRUCTURAL BASIS OF FORCE GENERATION BY THE MITOTIC MOTOR KINESIN-5.,Goulet A, Behnke-Parks WM, Sindelar CV, Major J, Rosenfeld SS, Moores C J Biol Chem. 2012 Nov 7. PMID:23135273<ref>PMID:23135273</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4aqw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Kinesin 3D Structures|Kinesin 3D Structures]]
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
== References ==
<references/>
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[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Behnke-Parks WM]]
[[Category: Goulet A]]
[[Category: Moores CA]]
[[Category: Rosenfeld SS]]
[[Category: Sindelar CV]]