Structural and functional insight into regulation of 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; null More Authors

doi:10.1126/science.abf6154

Structural and functional insight into regulation of 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, More Authors

^*Corresponding author for this work

ImPhys/Computational Imaging

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25 Citations (Scopus)

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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 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.

Original language	English
Article number	eabf6154
Pages (from-to)	326-+
Journal	Science
Volume	375
Issue number	6578
DOIs	https://doi.org/10.1126/science.abf6154
Publication status	Published - 2022

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Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care
Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.

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title = "Structural and functional insight into regulation of kinesin-1 by microtubule-associated protein MAP7",

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 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.",

author = "Ferro, {Luke S.} and Qianglin Fang and Lisa Eshun-Wilson and Jonathan Fernandes and Amanda Jack and Farrell, {Daniel P.} and Mert Golcuk and Teun Huijben and Katelyn Costa and {More Authors}",

note = "Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.",

year = "2022",

doi = "10.1126/science.abf6154",

language = "English",

volume = "375",

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T1 - Structural and functional insight into regulation of kinesin-1 by microtubule-associated protein MAP7

AU - Ferro, Luke S.

AU - Fang, Qianglin

AU - Eshun-Wilson, Lisa

AU - Fernandes, Jonathan

AU - Jack, Amanda

AU - Farrell, Daniel P.

AU - Golcuk, Mert

AU - Huijben, Teun

AU - Costa, Katelyn

AU - More Authors, null

N1 - Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

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JO - Science

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M1 - eabf6154

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

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