This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4uxy

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 17:25, 11 August 2016

Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins

Structural highlights

4uxy is a 3 chain structure with sequence from [1] and Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	4uxo, 4uxp, 4uxr, 4uxs, 4uxt, 4uy0
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[KIF5A_HUMAN] Autosomal dominant spastic paraplegia type 10;Autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation. The disease is caused by mutations affecting the gene represented in this entry.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Function

[TBA1B_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. [KIF5A_HUMAN] Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL) (By similarity). [TBB2B_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).

Publication Abstract from PubMed

Kinesins are a superfamily of microtubule-based ATP-powered motors, important for multiple, essential cellular functions. How microtubule binding stimulates their ATPase and controls force generation is not understood. To address this fundamental question, we visualized microtubule-bound kinesin-1 and kinesin-3 motor domains at multiple steps in their ATPase cycles - including their nucleotide-free states - at ~7A resolution using cryo-electron microscopy. In both motors, microtubule binding promotes ordered conformations of conserved loops that stimulate ADP release, enhance microtubule affinity and prime the catalytic site for ATP binding. ATP binding causes only small shifts of these nucleotide-coordinating loops but induces large conformational changes elsewhere that allow force generation and neck linker docking towards the microtubule plus end. Family-specific differences across the kinesin-microtubule interface account for the distinctive properties of each motor. Our data thus provide evidence for a conserved ATP-driven mechanism for kinesins and reveal the critical mechanistic contribution of the microtubule interface.

Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins.,Atherton J, Farabella I, Yu IM, Rosenfeld SS, Houdusse A, Topf M, Moores CA Elife. 2014 Sep 10:e03680. doi: 10.7554/eLife.03680. PMID:25209998^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Reid E, Kloos M, Ashley-Koch A, Hughes L, Bevan S, Svenson IK, Graham FL, Gaskell PC, Dearlove A, Pericak-Vance MA, Rubinsztein DC, Marchuk DA. A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am J Hum Genet. 2002 Nov;71(5):1189-94. Epub 2002 Sep 24. PMID:12355402 doi:http://dx.doi.org/10.1086/344210
↑ Fichera M, Lo Giudice M, Falco M, Sturnio M, Amata S, Calabrese O, Bigoni S, Calzolari E, Neri M. Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic paraplegia. Neurology. 2004 Sep 28;63(6):1108-10. PMID:15452312
↑ Lo Giudice M, Neri M, Falco M, Sturnio M, Calzolari E, Di Benedetto D, Fichera M. A missense mutation in the coiled-coil domain of the KIF5A gene and late-onset hereditary spastic paraplegia. Arch Neurol. 2006 Feb;63(2):284-7. PMID:16476820 doi:http://dx.doi.org/10.1001/archneur.63.2.284
↑ Blair MA, Ma S, Hedera P. Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia. Neurogenetics. 2006 Mar;7(1):47-50. Epub 2006 Feb 18. PMID:16489470 doi:http://dx.doi.org/10.1007/s10048-005-0027-8
↑ Ebbing B, Mann K, Starosta A, Jaud J, Schols L, Schule R, Woehlke G. Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity. Hum Mol Genet. 2008 May 1;17(9):1245-52. doi: 10.1093/hmg/ddn014. Epub 2008 Jan, 18. PMID:18203753 doi:http://dx.doi.org/10.1093/hmg/ddn014
↑ Schule R, Kremer BP, Kassubek J, Auer-Grumbach M, Kostic V, Klopstock T, Klimpe S, Otto S, Boesch S, van de Warrenburg BP, Schols L. SPG10 is a rare cause of spastic paraplegia in European families. J Neurol Neurosurg Psychiatry. 2008 May;79(5):584-7. doi:, 10.1136/jnnp.2007.137596. Epub 2008 Feb 1. PMID:18245137 doi:http://dx.doi.org/10.1136/jnnp.2007.137596
↑ Goizet C, Boukhris A, Mundwiller E, Tallaksen C, Forlani S, Toutain A, Carriere N, Paquis V, Depienne C, Durr A, Stevanin G, Brice A. Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10. Hum Mutat. 2009 Feb;30(2):E376-85. doi: 10.1002/humu.20920. PMID:18853458 doi:http://dx.doi.org/10.1002/humu.20920
↑ Musumeci O, Bassi MT, Mazzeo A, Grandis M, Crimella C, Martinuzzi A, Toscano A. A novel mutation in KIF5A gene causing hereditary spastic paraplegia with axonal neuropathy. Neurol Sci. 2011 Aug;32(4):665-8. doi: 10.1007/s10072-010-0445-8. Epub 2010 Nov, 24. PMID:21107874 doi:http://dx.doi.org/10.1007/s10072-010-0445-8
↑ Atherton J, Farabella I, Yu IM, Rosenfeld SS, Houdusse A, Topf M, Moores CA. Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins. Elife. 2014 Sep 10:e03680. doi: 10.7554/eLife.03680. PMID:25209998 doi:http://dx.doi.org/10.7554/eLife.03680

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4uxy"

@@ Line 1: / Line 1: @@
 ==Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins==
 <StructureSection load='4uxy' size='340' side='right' caption='[[4uxy]], [[Resolution|resolution]] 6.50&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uxo|4uxo]], [[4uxp|4uxp]], [[4uxr|4uxr]], [[4uxs|4uxs]], [[4uxt|4uxt]], [[4uy0|4uy0]]</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=4uxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uxy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uxy RCSB], [http://www.ebi.ac.uk/pdbsum/4uxy PDBsum]</span></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=4uxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uxy OCA], [http://pdbe.org/4uxy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uxy RCSB], [http://www.ebi.ac.uk/pdbsum/4uxy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uxy ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4uxy" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tubulin|Tubulin]]
 == References ==
 <references/>

4uxy

From Proteopedia

Revision as of 17:25, 11 August 2016

Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox