9ya7

KIF1A R350G bound to microtubules in the apo state

spinqualitylabelsall models 9ya7, resolution 3.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ya7 is a 3 chain structure with sequence from Homo sapiens and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.29Å Ligands: GDP, GTP, MG, TA1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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