4uxp: Difference between revisions

Revision as of 04:57, 11 May 2016

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

Structural highlights

4uxp 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:	ANP, GDP, GTP, MG, TA1, ZN
Related:	4uxo, 4uxr, 4uxs, 4uxt, 4uxy, 4uy0
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[KIF1A_HUMAN] Autosomal dominant nonsyndromic intellectual disability;Hereditary sensory and autonomic neuropathy type 2;Autosomal recessive spastic paraplegia type 30. The disease is caused by mutations affecting the gene represented in this entry.^[1] The disease is caused by mutations affecting the gene represented in this entry.^[2] The disease is caused by mutations affecting the gene represented in this entry.^[3]

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. [KIF1A_HUMAN] Motor for anterograde axonal transport of synaptic vesicle precursors (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^[4]

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

References

↑ Erlich Y, Edvardson S, Hodges E, Zenvirt S, Thekkat P, Shaag A, Dor T, Hannon GJ, Elpeleg O. Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Res. 2011 May;21(5):658-64. doi: 10.1101/gr.117143.110. Epub 2011 Apr 12. PMID:21487076 doi:https://dx.doi.org/10.1101/gr.117143.110
↑ Riviere JB, Ramalingam S, Lavastre V, Shekarabi M, Holbert S, Lafontaine J, Srour M, Merner N, Rochefort D, Hince P, Gaudet R, Mes-Masson AM, Baets J, Houlden H, Brais B, Nicholson GA, Van Esch H, Nafissi S, De Jonghe P, Reilly MM, Timmerman V, Dion PA, Rouleau GA. KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2. Am J Hum Genet. 2011 Aug 12;89(2):219-30. doi: 10.1016/j.ajhg.2011.06.013. Epub, 2011 Aug 4. PMID:21820098 doi:https://dx.doi.org/10.1016/j.ajhg.2011.06.013
↑ Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O, Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, D'Anjou G, Vanasse M, Srour M, Lafreniere RG, Drapeau P, Lacaille JC, Kim E, Lee JR, Igarashi K, Huganir RL, Rouleau GA, Michaud JL. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet. 2011 Mar 11;88(3):306-16. doi: 10.1016/j.ajhg.2011.02.001. Epub, 2011 Mar 3. PMID:21376300 doi:10.1016/j.ajhg.2011.02.001
↑ 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:https://dx.doi.org/10.7554/eLife.03680

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OCA

[1] Erlich Y, Edvardson S, Hodges E, Zenvirt S, Thekkat P, Shaag A, Dor T, Hannon GJ, Elpeleg O. Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Res. 2011 May;21(5):658-64. doi: 10.1101/gr.117143.110. Epub 2011 Apr 12. PMID:21487076 doi:https://dx.doi.org/10.1101/gr.117143.110

[2] Riviere JB, Ramalingam S, Lavastre V, Shekarabi M, Holbert S, Lafontaine J, Srour M, Merner N, Rochefort D, Hince P, Gaudet R, Mes-Masson AM, Baets J, Houlden H, Brais B, Nicholson GA, Van Esch H, Nafissi S, De Jonghe P, Reilly MM, Timmerman V, Dion PA, Rouleau GA. KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2. Am J Hum Genet. 2011 Aug 12;89(2):219-30. doi: 10.1016/j.ajhg.2011.06.013. Epub, 2011 Aug 4. PMID:21820098 doi:https://dx.doi.org/10.1016/j.ajhg.2011.06.013

[3] Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O, Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, D'Anjou G, Vanasse M, Srour M, Lafreniere RG, Drapeau P, Lacaille JC, Kim E, Lee JR, Igarashi K, Huganir RL, Rouleau GA, Michaud JL. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet. 2011 Mar 11;88(3):306-16. doi: 10.1016/j.ajhg.2011.02.001. Epub, 2011 Mar 3. PMID:21376300 doi:10.1016/j.ajhg.2011.02.001

[4] 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:https://dx.doi.org/10.7554/eLife.03680

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 ==Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins==
 <StructureSection load='4uxp' size='340' side='right' caption='[[4uxp]], [[Resolution|resolution]] 6.30&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=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>, <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]], [[4uxr|4uxr]], [[4uxs|4uxs]], [[4uxt|4uxt]], [[4uxy|4uxy]], [[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=4uxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uxp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uxp RCSB], [http://www.ebi.ac.uk/pdbsum/4uxp 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=4uxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uxp OCA], [http://pdbe.org/4uxp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uxp RCSB], [http://www.ebi.ac.uk/pdbsum/4uxp PDBsum]</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 4uxp" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tubulin|Tubulin]]
 == References ==
 <references/>

4uxp: Difference between revisions

Revision as of 04:57, 11 May 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?)

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