9L6K

Crystal structure of nucleotide-free human kinesin-1 motor domain (G234V mutant)

Summary for 9L6K

• Entry DOI: 10.2210/pdb9l6k/pdb
• Descriptor: Kinesin-1 heavy chain (1 entity in total)
• Functional Keywords: kinesin, motor protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 76668.05

Authors

Makino, T.,Miyazono, K.,Tanokura, M.,Tomishige, M. (deposition date: 2024-12-24, release date: 2025-04-23, Last modification date: 2025-05-21)

Primary citation

Makino, T.,Kanada, R.,Mori, T.,Miyazono, K.I.,Komori, Y.,Yanagisawa, H.,Takada, S.,Tanokura, M.,Kikkawa, M.,Tomishige, M.
Tension-induced suppression of allosteric conformational changes coordinates kinesin-1 stepping.
J.Cell Biol., 224:-, 2025

PubMed Abstract: Kinesin-1 walks along microtubules by alternating ATP hydrolysis and movement of its two motor domains ("head"). The detached head preferentially binds to the forward tubulin-binding site after ATP binds to the microtubule-bound head, but the mechanism preventing premature microtubule binding while the partner head awaits ATP remains unknown. Here, we examined the role of the neck linker, the segment connecting two heads, in this mechanism. Structural analyses of the nucleotide-free head revealed a bulge just ahead of the neck linker's base, creating an asymmetric constraint on its mobility. While the neck linker can stretch freely backward, it must navigate around this bulge to extend forward. We hypothesized that increased neck linker tension suppresses premature binding of the tethered head, which was supported by molecular dynamics simulations and single-molecule fluorescence assays. These findings demonstrate a tension-dependent allosteric mechanism that coordinates the movement of two heads, where neck linker tension modulates the allosteric conformational changes rather than directly affecting the nucleotide state.

PubMed: 40298806
DOI: 10.1083/jcb.202501253

Experimental method

X-RAY DIFFRACTION (2.8 Å)