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.
7eob
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
==Crystal structure of KIF1A Motor-Neck domain E239K mutant with ADP-Mg-AlFx== | ==Crystal structure of KIF1A Motor-Neck domain E239K mutant with ADP-Mg-AlFx== | ||
| - | <StructureSection load='7eob' size='340' side='right'caption='[[7eob]]' scene=''> | + | <StructureSection load='7eob' size='340' side='right'caption='[[7eob]], [[Resolution|resolution]] 1.76Å' 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=7EOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EOB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7eob]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EOB 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=7eob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eob OCA], [https://pdbe.org/7eob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eob RCSB], [https://www.ebi.ac.uk/pdbsum/7eob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eob 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=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7eob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eob OCA], [https://pdbe.org/7eob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eob RCSB], [https://www.ebi.ac.uk/pdbsum/7eob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eob ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/KIF1A_MOUSE KIF1A_MOUSE]] Motor for anterograde axonal transport of synaptic vesicle precursors. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The mechanochemical coupling of ATPase hydrolysis and conformational dynamics in kinesin motors facilitates intramolecular interaction cycles between the kinesin motor and neck domains, which are essential for microtubule-based motility. Here, we characterized a charge-inverting KIF1A-E239K mutant that we identified in a family with axonal-type Charcot-Marie-Tooth disease and also in 24 cases in human neuropathies including spastic paraplegia and hereditary sensory and autonomic neuropathy. We show that Glu239 in the beta7 strand is a key residue of the motor domain that regulates the motor-neck interaction. Expression of the KIF1A-E239K mutation has decreased ability to complement Kif1a(+/-) neurons, and significantly decreases ATPase activity and microtubule gliding velocity. X-ray crystallography shows that this mutation causes an excess positive charge on beta7, which may electrostatically interact with a negative charge on the neck. Quantitative mass spectrometric analysis supports that the mutation hyper-stabilizes the motor-neck interaction at the late ATP hydrolysis stage. Thus, the negative charge of Glu239 dynamically regulates the kinesin motor-neck interaction, promoting release of the neck from the motor domain upon ATP hydrolysis. | ||
| + | |||
| + | A neuropathy-associated kinesin KIF1A mutation hyper-stabilizes the motor-neck interaction during the ATPase cycle.,Morikawa M, Jerath NU, Ogawa T, Morikawa M, Tanaka Y, Shy ME, Zuchner S, Hirokawa N EMBO J. 2022 Mar 1;41(5):e108899. doi: 10.15252/embj.2021108899. Epub 2022 Feb 8. PMID:35132656<ref>PMID:35132656</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7eob" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Hirokawa N]] | + | [[Category: Hirokawa, N]] |
| - | [[Category: Jiang X]] | + | [[Category: Jiang, X]] |
| - | [[Category: Ogawa T]] | + | [[Category: Ogawa, T]] |
| + | [[Category: Kinesin]] | ||
| + | [[Category: Motor protein]] | ||
Revision as of 07:17, 9 March 2022
Crystal structure of KIF1A Motor-Neck domain E239K mutant with ADP-Mg-AlFx
| |||||||||||
