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

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*

*Bu çalışma için yazışmadan sorumlu yazar

Araştırma sonucu: ???type-name???Makalebilirkişi

38 Atıf (Scopus)

Özet

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 a 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.

Orijinal dilİngilizce
Makale numarasıeabf6154
DergiScience
Hacim375
Basın numarası6578
DOI'lar
Yayın durumuYayınlandı - 21 Oca 2022

Bibliyografik not

Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

Finansman

This work was supported by grants from the National Institute of General Medical Sciences (GM094522 (A.Y.), GM123655-03 (L.F.), GM051487 (E.N.), GM127018 (E.N.), and the National Science Foundation (MCB-1617028 and MCB-1055017, A.Y.), PRACE (2019215144, MG), and Istanbul Technical University BAP (MGA-2021-42803, MG). E.N. is a Howard Hughes Medical Institute Investigator.

FinansörlerFinansör numarası
National Science FoundationMCB-1617028, MCB-1055017
National Institute of General Medical SciencesGM051487, R01GM123089, GM094522, GM123655-03, GM127018
Partnership for Advanced Computing in Europe AISBL2019215144
Istanbul Teknik ÜniversitesiMGA-2021-42803

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