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Title | Structural and functional insight into regulation of kinesin-1 by microtubule-associated protein MAP7. |
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Journal, issue, pages | Science, Vol. 375, Issue 6578, Page 326-331, Year 2022 |
Publish date | Jan 21, 2022 |
Authors | Luke S Ferro / Qianglin Fang / Lisa Eshun-Wilson / Jonathan Fernandes / Amanda Jack / Daniel P Farrell / Mert Golcuk / Teun Huijben / Katelyn Costa / Mert Gur / Frank DiMaio / Eva Nogales / Ahmet Yildiz / |
PubMed Abstract | Microtubule (MT)-associated protein 7 (MAP7) is a required cofactor for kinesin-1-driven transport of intracellular cargoes. Using cryo-electron microscopy and single-molecule imaging, we ...Microtubule (MT)-associated protein 7 (MAP7) is a required cofactor for kinesin-1-driven transport of intracellular cargoes. Using cryo-electron microscopy and single-molecule imaging, we investigated how MAP7 binds MTs and facilitates kinesin-1 motility. The MT-binding domain (MTBD) of MAP7 bound MTs as an extended α helix between the protofilament ridge and the site of lateral contact. Unexpectedly, the MTBD partially overlapped with the binding site of kinesin-1 and inhibited its motility. However, by tethering kinesin-1 to the MT, the projection domain of MAP7 prevented dissociation of the motor and facilitated its binding to available neighboring sites. The inhibitory effect of the MTBD dominated as MTs became saturated with MAP7. Our results reveal biphasic regulation of kinesin-1 by MAP7 in the context of their competitive binding to MTs. |
External links | Science / PubMed:35050657 / PubMed Central |
Methods | EM (helical sym.) / EM (single particle) |
Resolution | 3.3 - 4.2 Å |
Structure data | EMDB-25117: Cryo-EM reconstruction of MAP7 83-134, bound to the microtubule EMDB-25118: Cryo-EM reconstruction of Kinesin-1 and MAP7, bound to the microtubule EMDB-25119: Cryo-EM structure of MAP7 MTBD and microtubule-associated protein tau, bound to the microtubule EMDB-25120, PDB-7sgs: |
Chemicals | ChemComp-GTP: ChemComp-MG: ChemComp-GDP: |
Source |
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Keywords | STRUCTURAL PROTEIN / microtubule / microtubule-associated protein / cytoskeleton |