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Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate

Kinesin-13 proteins are major microtubule (MT) regulatory factors that catalyze removal of tubulin subunits from MT ends. The class-specific “neck” and loop 2 regions of these motors are required for MT depolymerization, but their contributing roles are still unresolved because their interactions wi...

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Autores principales: Trofimova, Daria, Paydar, Mohammadjavad, Zara, Anthony, Talje, Lama, Kwok, Benjamin H., Allingham, John S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035175/
https://www.ncbi.nlm.nih.gov/pubmed/29980677
http://dx.doi.org/10.1038/s41467-018-05025-7
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author Trofimova, Daria
Paydar, Mohammadjavad
Zara, Anthony
Talje, Lama
Kwok, Benjamin H.
Allingham, John S.
author_facet Trofimova, Daria
Paydar, Mohammadjavad
Zara, Anthony
Talje, Lama
Kwok, Benjamin H.
Allingham, John S.
author_sort Trofimova, Daria
collection PubMed
description Kinesin-13 proteins are major microtubule (MT) regulatory factors that catalyze removal of tubulin subunits from MT ends. The class-specific “neck” and loop 2 regions of these motors are required for MT depolymerization, but their contributing roles are still unresolved because their interactions with MT ends have not been observed directly. Here we report the crystal structure of a catalytically active kinesin-13 monomer (Kif2A) in complex with two bent αβ-tubulin heterodimers in a head-to-tail array, providing a view of these interactions. The neck of Kif2A binds to one tubulin dimer and the motor core to the other, guiding insertion of the KVD motif of loop 2 in between them. AMPPNP-bound Kif2A can form stable complexes with tubulin in solution and trigger MT depolymerization. We also demonstrate the importance of the neck in modulating ATP turnover and catalytic depolymerization of MTs. These results provide mechanistic insights into the catalytic cycles of kinesin-13.
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spelling pubmed-60351752018-07-09 Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate Trofimova, Daria Paydar, Mohammadjavad Zara, Anthony Talje, Lama Kwok, Benjamin H. Allingham, John S. Nat Commun Article Kinesin-13 proteins are major microtubule (MT) regulatory factors that catalyze removal of tubulin subunits from MT ends. The class-specific “neck” and loop 2 regions of these motors are required for MT depolymerization, but their contributing roles are still unresolved because their interactions with MT ends have not been observed directly. Here we report the crystal structure of a catalytically active kinesin-13 monomer (Kif2A) in complex with two bent αβ-tubulin heterodimers in a head-to-tail array, providing a view of these interactions. The neck of Kif2A binds to one tubulin dimer and the motor core to the other, guiding insertion of the KVD motif of loop 2 in between them. AMPPNP-bound Kif2A can form stable complexes with tubulin in solution and trigger MT depolymerization. We also demonstrate the importance of the neck in modulating ATP turnover and catalytic depolymerization of MTs. These results provide mechanistic insights into the catalytic cycles of kinesin-13. Nature Publishing Group UK 2018-07-06 /pmc/articles/PMC6035175/ /pubmed/29980677 http://dx.doi.org/10.1038/s41467-018-05025-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Trofimova, Daria
Paydar, Mohammadjavad
Zara, Anthony
Talje, Lama
Kwok, Benjamin H.
Allingham, John S.
Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate
title Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate
title_full Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate
title_fullStr Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate
title_full_unstemmed Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate
title_short Ternary complex of Kif2A-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate
title_sort ternary complex of kif2a-bound tandem tubulin heterodimers represents a kinesin-13-mediated microtubule depolymerization reaction intermediate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035175/
https://www.ncbi.nlm.nih.gov/pubmed/29980677
http://dx.doi.org/10.1038/s41467-018-05025-7
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