View source for 9yab


==KIF1A R350W bound to microtubules in the apo state==
<StructureSection load='9yab' size='340' side='right'caption='[[9yab]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9yab]] is a 3 chain structure with sequence from [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=9YAB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YAB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.21&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=9yab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9yab OCA], [https://pdbe.org/9yab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9yab RCSB], [https://www.ebi.ac.uk/pdbsum/9yab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9yab ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TBA1B_PIG TBA1B_PIG] 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pathogenic variants in the motor domain of the kinesin-3 motor protein KIF1A cause a range of neurodevelopmental and neurodegenerative conditions collectively termed KIF1A-associated neurological disorder (KAND). Among these, mutations at residue R350 are linked to hereditary spastic paraplegia and altered motor function. Yet, the structural basis for their pathogenicity remains unclear. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of KIF1A R350G and R350W bound to microtubules in both the apo and AMP-PNP-bound states. We identify a salt bridge between KIF1A residue R350 and alpha-tubulin E415 that forms only in the open conformation of the motor domain and is disrupted in both mutants. The loss of this electrostatic interaction correlates with increased velocity, reduced processivity, and decreased microtubule affinity in the open, apo conformation, as demonstrated by single-molecule assays. Our results reveal an electrostatic interaction at the motor-microtubule interface that regulates KIF1A's motility behavior.

Pathogenic KIF1A R350 mutations disrupt a conserved and conformation-dependent kinesin-tubulin salt bridge.,Shatarupa A, Rao L, Asenjo AB, Gennerich A, Sosa H Nat Commun. 2026 Mar 31. doi: 10.1038/s41467-026-71026-6. PMID:41912506<ref>PMID:41912506</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9yab" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Asenjo AB]]
[[Category: Gennerich A]]
[[Category: Rao L]]
[[Category: Shatarupa A]]
[[Category: Sosa H]]