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-Structure paper
Title | Interplay between the Kinesin and Tubulin Mechanochemical Cycles Underlies Microtubule Tip Tracking by the Non-motile Ciliary Kinesin Kif7. |
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Journal, issue, pages | Dev Cell, Vol. 49, Issue 5, Page 711-730.e8, Year 2019 |
Publish date | Jun 3, 2019 |
Authors | Shuo Jiang / Nandini Mani / Elizabeth M Wilson-Kubalek / Pei-I Ku / Ronald A Milligan / Radhika Subramanian / |
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 ...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. |
External links | Dev Cell / PubMed:31031197 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 4.2 Å |
Structure data | |
Chemicals | ChemComp-MG: ChemComp-GTP: ChemComp-GDP: ChemComp-TA1: ChemComp-ADP: ChemComp-ANP: |
Source |
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Keywords | MOTOR PROTEIN / Microtubule tip-tracking / Primary cilium / Hedgehog signaling / motor protein/inhibitor / motor protein-inhibitor complex |