A structural and dynamic visualization of the interaction between MAP7 and microtubules

Agnes Adler; Mamata Bangera; J Wouter Beugelink; Salima Bahri; Hugo van Ingen; Carolyn A Moores; Marc Baldus

doi:10.1038/s41467-024-46260-5

A structural and dynamic visualization of the interaction between MAP7 and microtubules

Agnes Adler, Mamata Bangera, J Wouter Beugelink, Salima Bahri, Hugo van Ingen, Carolyn A Moores^*, Marc Baldus^*

^*Corresponding author for this work

University of London

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Microtubules (MTs) are key components of the eukaryotic cytoskeleton and are essential for intracellular organization, organelle trafficking and mitosis. MT tasks depend on binding and interactions with MT-associated proteins (MAPs). MT-associated protein 7 (MAP7) has the unusual ability of both MT binding and activating kinesin-1-mediated cargo transport along MTs. Additionally, the protein is reported to stabilize MTs with its 112 amino-acid long MT-binding domain (MTBD). Here we investigate the structural basis of the interaction of MAP7 MTBD with the MT lattice. Using a combination of solid and solution-state nuclear magnetic resonance (NMR) spectroscopy with electron microscopy, fluorescence anisotropy and isothermal titration calorimetry, we shed light on the binding mode of MAP7 to MTs at an atomic level. Our results show that a combination of interactions between MAP7 and MT lattice extending beyond a single tubulin dimer and including tubulin C-terminal tails contribute to formation of the MAP7-MT complex.

Original language	English
Article number	1948
Number of pages	16
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-46260-5
Publication status	Published - 2 Mar 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Funding

This work was supported by NWO (the Dutch Science Foundation) via a TOP-PUNT (grant number 718.015.001) grant to M.B., by uNMR-NL, the National Roadmap Large-Scale NMR Facility of the Netherlands (grant number 184.032.207 to M.B.), the uNMR-NL grid (grant number 184.035.002 to M.B.) and by Medical Research Council, U.K. (MR/R00352/1) to C.A.M. We acknowledge Diamond Light Source for access and support of the cryo-EM facilities at the UK’s national Electron Bio-imaging Centre (eBIC) funder proposal EM20287-56, funded by the Wellcome Trust, MRC and BBSRC. Cryo-EM data for the final EM reconstructions were collected at ISMB EM facility (Birkbeck College, University of London) with financial support from the Wellcome Trust (202679/Z/16/Z and 206166/Z/17/Z). We thank N. Lukoyanova and S. Chen for electron microscope support and D. Houldershaw for computational support at Birkbeck. M.B. and C.A.M. acknowledge J. Atherton’s initial contributions in electron microscopy studies of MAP7 MTBD with microtubules. A.A. and M.B. would like to thank Anna Akhmanova for providing the MAP7 construct and for scientific discussions. A.A. thanks Dr. U. B. le Paige for fruitful discussions and ideas. This work was supported by NWO (the Dutch Science Foundation) via a TOP-PUNT (grant number 718.015.001) grant to M.B., by uNMR-NL, the National Roadmap Large-Scale NMR Facility of the Netherlands (grant number 184.032.207 to M.B.), the uNMR-NL grid (grant number 184.035.002 to M.B.) and by Medical Research Council, U.K. (MR/R00352/1) to C.A.M. We acknowledge Diamond Light Source for access and support of the cryo-EM facilities at the UK’s national Electron Bio-imaging Centre (eBIC) funder proposal EM20287-56, funded by the Wellcome Trust, MRC and BBSRC. Cryo-EM data for the final EM reconstructions were collected at ISMB EM facility (Birkbeck College, University of London) with financial support from the Wellcome Trust (202679/Z/16/Z and 206166/Z/17/Z). We thank N. Lukoyanova and S. Chen for electron microscope support and D. Houldershaw for computational support at Birkbeck. M.B. and C.A.M. acknowledge J. Atherton’s initial contributions in electron microscopy studies of MAP7 MTBD with microtubules. A.A. and M.B. would like to thank Anna Akhmanova for providing the MAP7 construct and for scientific discussions. A.A. thanks Dr. U. B. le Paige for fruitful discussions and ideas.

Funders	Funder number
Anna Akhmanova
Birkbeck College, University of London	206166/Z/17/Z, 202679/Z/16/Z
TOP-PUNT	184.035.002, 184.032.207, 718.015.001
Wellcome Trust
Medical Research Council	EM20287-56, MR/R00352/1
Medical Research Council
Biotechnology and Biological Sciences Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Keywords

Humans
Kinesins/metabolism
Microtubule-Associated Proteins/metabolism
Microtubules/metabolism
Organelles/metabolism
Tubulin/metabolism

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title = "A structural and dynamic visualization of the interaction between MAP7 and microtubules",

abstract = "Microtubules (MTs) are key components of the eukaryotic cytoskeleton and are essential for intracellular organization, organelle trafficking and mitosis. MT tasks depend on binding and interactions with MT-associated proteins (MAPs). MT-associated protein 7 (MAP7) has the unusual ability of both MT binding and activating kinesin-1-mediated cargo transport along MTs. Additionally, the protein is reported to stabilize MTs with its 112 amino-acid long MT-binding domain (MTBD). Here we investigate the structural basis of the interaction of MAP7 MTBD with the MT lattice. Using a combination of solid and solution-state nuclear magnetic resonance (NMR) spectroscopy with electron microscopy, fluorescence anisotropy and isothermal titration calorimetry, we shed light on the binding mode of MAP7 to MTs at an atomic level. Our results show that a combination of interactions between MAP7 and MT lattice extending beyond a single tubulin dimer and including tubulin C-terminal tails contribute to formation of the MAP7-MT complex.",

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AU - Beugelink, J Wouter

AU - Bahri, Salima

AU - van Ingen, Hugo

AU - Moores, Carolyn A

AU - Baldus, Marc

N1 - Publisher Copyright: © The Author(s) 2024.

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A structural and dynamic visualization of the interaction between MAP7 and microtubules

Abstract

Bibliographical note

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Keywords

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