Structural and functional insight into regulation of kinesin-1 by microtubule-associated protein MAP7

Ferro L. S., Fang Q., Eshun-Wilson L., Fernandes J., Jack A., Farrell D. P., ...More

SCIENCE, vol.375, no.6578, pp.326-367, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 375 Issue: 6578
  • Publication Date: 2022
  • Doi Number: 10.1126/science.abf6154
  • Journal Name: SCIENCE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Agricultural & Environmental Science Database, Animal Behavior Abstracts, Applied Science & Technology Source, Aquatic Science & Fisheries Abstracts (ASFA), Artic & Antarctic Regions, ATLA Religion Database, BIOSIS, CAB Abstracts, Communication Abstracts, Computer & Applied Sciences, EBSCO Education Source, EMBASE, Environment Index, Gender Studies Database, Geobase, Linguistic Bibliography, MEDLINE, Metadex, MLA - Modern Language Association Database, Pollution Abstracts, Psycinfo, Public Affairs Index, Sociological abstracts, Veterinary Science Database, zbMATH, DIALNET, Civil Engineering Abstracts
  • Page Numbers: pp.326-367
  • Istanbul Technical University Affiliated: Yes

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 investigated how MAP7 binds MTs and facilitates kinesin-1 motility. The MT-binding domain (MTBD) of MAP7 bound MTs as an extended alpha 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.