5lt3: Difference between revisions
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==nucleotide-free kinesin-1 motor domain T87A mutant, P1 crystal form== | |||
<StructureSection load='5lt3' size='340' side='right' caption='[[5lt3]], [[Resolution|resolution]] 2.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5lt3]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LT3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LT3 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5lt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lt3 OCA], [http://pdbe.org/5lt3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lt3 RCSB], [http://www.ebi.ac.uk/pdbsum/5lt3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lt3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/KINH_HUMAN KINH_HUMAN]] Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Kinesin-1 is an ATP-dependent motor protein that moves towards microtubules (+)-ends. Whereas structures of isolated ADP-kinesin and of complexes with tubulin of apo-kinesin and of ATP-like-kinesin are available, structural data on apo-kinesin-1 in the absence of tubulin are still missing, leaving the role of nucleotide release in the structural cycle unsettled. Here, we identified mutations in the kinesin nucleotide-binding P-loop motif that interfere with ADP binding. These mutations destabilize the P-loop (T87A mutant) or magnesium binding (T92V), highlighting a dual mechanism for nucleotide release. The structures of these mutants in their apo form are either isomorphous to ADP-kinesin-1 or to tubulin-bound apo-kinesin-1. Remarkably, both structures are also obtained from the nucleotide-depleted wild-type protein. Our results lead to a model in which, when detached from microtubules, apo-kinesin possibly occupies the two conformations we characterized, whereas, upon microtubule binding, ADP-kinesin converts to the tubulin-bound apo-kinesin conformation and releases ADP. This conformation is primed to bind ATP and, therefore, to run through the natural nucleotide cycle of kinesin-1. | |||
The structural switch of nucleotide-free kinesin.,Cao L, Cantos-Fernandes S, Gigant B Sci Rep. 2017 Feb 14;7:42558. doi: 10.1038/srep42558. PMID:28195215<ref>PMID:28195215</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5lt3" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cao, L]] | |||
[[Category: Gigant, B]] | |||
[[Category: Adp dissociation]] | |||
[[Category: Kinesin motor domain]] | |||
[[Category: Motor protein]] | |||
[[Category: Nucleotide-free]] | |||
Revision as of 12:37, 11 March 2017
nucleotide-free kinesin-1 motor domain T87A mutant, P1 crystal formnucleotide-free kinesin-1 motor domain T87A mutant, P1 crystal form
Structural highlights
Function[KINH_HUMAN] Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes (By similarity). Publication Abstract from PubMedKinesin-1 is an ATP-dependent motor protein that moves towards microtubules (+)-ends. Whereas structures of isolated ADP-kinesin and of complexes with tubulin of apo-kinesin and of ATP-like-kinesin are available, structural data on apo-kinesin-1 in the absence of tubulin are still missing, leaving the role of nucleotide release in the structural cycle unsettled. Here, we identified mutations in the kinesin nucleotide-binding P-loop motif that interfere with ADP binding. These mutations destabilize the P-loop (T87A mutant) or magnesium binding (T92V), highlighting a dual mechanism for nucleotide release. The structures of these mutants in their apo form are either isomorphous to ADP-kinesin-1 or to tubulin-bound apo-kinesin-1. Remarkably, both structures are also obtained from the nucleotide-depleted wild-type protein. Our results lead to a model in which, when detached from microtubules, apo-kinesin possibly occupies the two conformations we characterized, whereas, upon microtubule binding, ADP-kinesin converts to the tubulin-bound apo-kinesin conformation and releases ADP. This conformation is primed to bind ATP and, therefore, to run through the natural nucleotide cycle of kinesin-1. The structural switch of nucleotide-free kinesin.,Cao L, Cantos-Fernandes S, Gigant B Sci Rep. 2017 Feb 14;7:42558. doi: 10.1038/srep42558. PMID:28195215[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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