7tr1: Difference between revisions
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==== | ==CaKip3[2-436]-L2-mutant(HsKHC) - AMP-PNP in complex with a microtubule== | ||
<StructureSection load='7tr1' size='340' side='right'caption='[[7tr1]]' scene=''> | <StructureSection load='7tr1' size='340' side='right'caption='[[7tr1]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7tr1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans Candida albicans], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7TR1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TR1 FirstGlance]. <br> | ||
</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=7tr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tr1 OCA], [https://pdbe.org/7tr1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tr1 RCSB], [https://www.ebi.ac.uk/pdbsum/7tr1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tr1 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <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=7tr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tr1 OCA], [https://pdbe.org/7tr1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tr1 RCSB], [https://www.ebi.ac.uk/pdbsum/7tr1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tr1 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/C4YNU9_CANAW C4YNU9_CANAW]] [[https://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-8s are dual-activity motor proteins that can move processively on microtubules and depolymerize microtubule plus-ends, but their mechanism of combining these distinct activities remains unclear. We addressed this by obtaining cryo-EM structures (2.6-3.9 A) of Candida albicans Kip3 in different catalytic states on the microtubule lattice and on a curved microtubule end mimic. We also determined a crystal structure of microtubule-unbound CaKip3-ADP (2.0 A) and analyzed the biochemical activity of CaKip3 and kinesin-1 mutants. These data reveal that the microtubule depolymerization activity of kinesin-8 originates from conformational changes of its motor core that are amplified by dynamic contacts between its extended loop-2 and tubulin. On curved microtubule ends, loop-1 inserts into preceding motor domains, forming head-to-tail arrays of kinesin-8s that complement loop-2 contacts with curved tubulin and assist depolymerization. On straight tubulin protofilaments in the microtubule lattice, loop-2-tubulin contacts inhibit conformational changes in the motor core, but in the ADP-Pi state these contacts are relaxed, allowing neck-linker docking for motility. We propose that these tubulin shape-induced alternations between pro-microtubule-depolymerization and pro-motility kinesin states, regulated by loop-2, are the key to the dual activity of kinesin-8 motors. | |||
Kinesin-8-specific loop-2 controls the dual activities of the motor domain according to tubulin protofilament shape.,Hunter B, Benoit MPMH, Asenjo AB, Doubleday C, Trofimova D, Frazer C, Shoukat I, Sosa H, Allingham JS Nat Commun. 2022 Jul 20;13(1):4198. doi: 10.1038/s41467-022-31794-3. PMID:35859148<ref>PMID:35859148</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7tr1" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Candida albicans]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Sus scrofa]] | ||
[[Category: Allingham JS]] | |||
[[Category: Asenjo AB]] | |||
[[Category: Benoit MPMH]] | |||
[[Category: Hunter B]] | |||
[[Category: Sosa H]] | |||
Revision as of 07:59, 8 September 2022
CaKip3[2-436]-L2-mutant(HsKHC) - AMP-PNP in complex with a microtubuleCaKip3[2-436]-L2-mutant(HsKHC) - AMP-PNP in complex with a microtubule
Structural highlights
Function[C4YNU9_CANAW] [KINH_HUMAN] Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes (By similarity). Publication Abstract from PubMedKinesin-8s are dual-activity motor proteins that can move processively on microtubules and depolymerize microtubule plus-ends, but their mechanism of combining these distinct activities remains unclear. We addressed this by obtaining cryo-EM structures (2.6-3.9 A) of Candida albicans Kip3 in different catalytic states on the microtubule lattice and on a curved microtubule end mimic. We also determined a crystal structure of microtubule-unbound CaKip3-ADP (2.0 A) and analyzed the biochemical activity of CaKip3 and kinesin-1 mutants. These data reveal that the microtubule depolymerization activity of kinesin-8 originates from conformational changes of its motor core that are amplified by dynamic contacts between its extended loop-2 and tubulin. On curved microtubule ends, loop-1 inserts into preceding motor domains, forming head-to-tail arrays of kinesin-8s that complement loop-2 contacts with curved tubulin and assist depolymerization. On straight tubulin protofilaments in the microtubule lattice, loop-2-tubulin contacts inhibit conformational changes in the motor core, but in the ADP-Pi state these contacts are relaxed, allowing neck-linker docking for motility. We propose that these tubulin shape-induced alternations between pro-microtubule-depolymerization and pro-motility kinesin states, regulated by loop-2, are the key to the dual activity of kinesin-8 motors. Kinesin-8-specific loop-2 controls the dual activities of the motor domain according to tubulin protofilament shape.,Hunter B, Benoit MPMH, Asenjo AB, Doubleday C, Trofimova D, Frazer C, Shoukat I, Sosa H, Allingham JS Nat Commun. 2022 Jul 20;13(1):4198. doi: 10.1038/s41467-022-31794-3. PMID:35859148[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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