6MLR

Cryo-EM structure of microtubule-bound Kif7 in the AMPPNP state

Summary for 6MLR

• Entry DOI: 10.2210/pdb6mlr/pdb
• EMDB information: 9141
• Descriptor: Tubulin alpha-1A chain, Tubulin beta chain, Kinesin-like protein KIF7, ... (7 entities in total)
• Functional Keywords: microtubule tip-tracking, primary cilium, hedgehog signaling, motor protein, motor protein-inhibitor complex, motor protein/inhibitor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 146018.78

Authors

Mani, N.,Jiang, S.,Wilson-Kubalek, E.M.,Ku, P.,Milligan, R.A.,Subramanian, R. (deposition date: 2018-09-27, release date: 2019-05-01, Last modification date: 2024-03-13)

Primary citation

Jiang, S.,Mani, N.,Wilson-Kubalek, E.M.,Ku, P.I.,Milligan, R.A.,Subramanian, R.
Interplay between the Kinesin and Tubulin Mechanochemical Cycles Underlies Microtubule Tip Tracking by the Non-motile Ciliary Kinesin Kif7.
Dev.Cell, 49:711-730.e8, 2019

PubMed Abstract: The correct localization of Hedgehog effectors to the tip of primary cilia is critical for proper signal transduction. The conserved non-motile kinesin Kif7 defines a "cilium-tip compartment" by localizing to the distal ends of axonemal microtubules. How Kif7 recognizes microtubule ends remains unknown. We find that Kif7 preferentially binds GTP-tubulin at microtubule ends over GDP-tubulin in the mature microtubule lattice, and ATP hydrolysis by Kif7 enhances this discrimination. Cryo-electron microscopy (cryo-EM) structures suggest that a rotated microtubule footprint and conformational changes in the ATP-binding pocket underlie Kif7's atypical microtubule-binding properties. Finally, Kif7 not only recognizes but also stabilizes a GTP-form of tubulin to promote its own microtubule-end localization. Thus, unlike the characteristic microtubule-regulated ATPase activity of kinesins, Kif7 modulates the tubulin mechanochemical cycle. We propose that the ubiquitous kinesin fold has been repurposed in Kif7 to facilitate organization of a spatially restricted platform for localization of Hedgehog effectors at the cilium tip.

PubMed: 31031197
DOI: 10.1016/j.devcel.2019.04.001

Experimental method

ELECTRON MICROSCOPY (4.2 Å)