A highly conserved 310 helix within the kinesin motor domain is critical for kinesin function and human health

Aileen J. Lam, Lu Rao, Yuzu Anazawa, Kyoko Okada, Kyoko Chiba, Mariah Dacy, Shinsuke Niwa, Arne Gennerich, Dan W. Nowakowski, Richard J. McKenney

Research output: Contribution to journalArticlepeer-review


KIF1A is a critical cargo transport motor within neurons. More than 100 known mutations result in KIF1A-associated neurological disorder (KAND), a degenerative condition for which there is no cure. A missense mutation, P305L, was identified in children diagnosed with KAND, but the molecular basis for the disease is unknown. We find that this conserved residue is part of an unusual 310 helix immediately adjacent to the family-specific K-loop, which facilitates a high microtubule-association rate. We find that the mutation negatively affects several biophysical parameters of the motor. However, the microtubule-association rate of the motor is most markedly affected, revealing that the presence of an intact K-loop is not sufficient for its function. We hypothesize that the 310 helix facilitates a specific K-loop conformation that is critical for its function. We find that the function of this proline is conserved in kinesin-1, revealing a fundamental principle of the kinesin motor mechanism.

Original languageEnglish (US)
Article numbereabf1002
JournalScience Advances
Issue number18
StatePublished - Apr 2021

ASJC Scopus subject areas

  • General


Dive into the research topics of 'A highly conserved 3<sub>10</sub> helix within the kinesin motor domain is critical for kinesin function and human health'. Together they form a unique fingerprint.

Cite this