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TitleStructural and functional insight into regulation of kinesin-1 by microtubule-associated protein MAP7.
Journal, issue, pagesScience, Vol. 375, Issue 6578, Page 326-331, Year 2022
Publish dateJan 21, 2022
AuthorsLuke 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 AbstractMicrotubule (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 linksScience / PubMed:35050657 / PubMed Central
MethodsEM (helical sym.) / EM (single particle)
Resolution3.3 - 4.2 Å
Structure data

EMDB-25117: Cryo-EM reconstruction of MAP7 83-134, bound to the microtubule
Method: EM (helical sym.) / Resolution: 3.7 Å

EMDB-25118: Cryo-EM reconstruction of Kinesin-1 and MAP7, bound to the microtubule
Method: EM (helical sym.) / Resolution: 4.2 Å

EMDB-25119: Cryo-EM structure of MAP7 MTBD and microtubule-associated protein tau, bound to the microtubule
Method: EM (helical sym.) / Resolution: 4.0 Å

EMDB-25120, PDB-7sgs:
Cryo-EM structure of full-length MAP7 bound to the microtubule
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

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

ChemComp-MG:
Unknown entry

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

Source
  • sus scrofa (pig)
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / microtubule / microtubule-associated protein / cytoskeleton

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