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TitleInterplay between the Kinesin and Tubulin Mechanochemical Cycles Underlies Microtubule Tip Tracking by the Non-motile Ciliary Kinesin Kif7.
Journal, issue, pagesDev Cell, Vol. 49, Issue 5, Page 711-730.e8, Year 2019
Publish dateJun 3, 2019
AuthorsShuo Jiang / Nandini Mani / Elizabeth M Wilson-Kubalek / Pei-I Ku / Ronald A Milligan / Radhika Subramanian /
PubMed AbstractThe 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 linksDev Cell / PubMed:31031197 / PubMed Central
MethodsEM (helical sym.)
Resolution4.2 Å
Structure data

9140

6mlq

EMDB-9140, PDB-6mlq:
Cryo-EM structure of microtubule-bound Kif7 in the ADP state
Method: EM (helical sym.) / Resolution: 4.2 Å

9141

6mlr

EMDB-9141, PDB-6mlr:
Cryo-EM structure of microtubule-bound Kif7 in the AMPPNP state
Method: EM (helical sym.) / Resolution: 4.2 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM / Guanosine diphosphate

ChemComp-TA1:
TAXOL / medication, chemotherapy*YM / Paclitaxel

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
  • sus scrofa (pig)
KeywordsMOTOR PROTEIN / Microtubule tip-tracking / Primary cilium / Hedgehog signaling / motor protein/inhibitor / motor protein-inhibitor complex

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