Modular assembly of the principal microtubule nucleator γ-TuRC
Martin Würtz,
Erik Zupa,
Enrico S. Atorino,
Annett Neuner,
Anna Böhler,
Ariani S. Rahadian,
Bram J. A. Vermeulen,
Giulia Tonon,
Sebastian Eustermann,
Elmar Schiebel () and
Stefan Pfeffer ()
Additional contact information
Martin Würtz: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Erik Zupa: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Enrico S. Atorino: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Annett Neuner: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Anna Böhler: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Ariani S. Rahadian: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Bram J. A. Vermeulen: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Giulia Tonon: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Sebastian Eustermann: European Molecular Biology Laboratory (EMBL)
Elmar Schiebel: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Stefan Pfeffer: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz
Nature Communications, 2022, vol. 13, issue 1, 1-16
Abstract:
Abstract The gamma-tubulin ring complex (γ-TuRC) is the principal microtubule nucleation template in vertebrates. Recent cryo-EM reconstructions visualized the intricate quaternary structure of the γ-TuRC, containing more than thirty subunits, raising fundamental questions about γ-TuRC assembly and the role of actin as an integral part of the complex. Here, we reveal the structural mechanism underlying modular γ-TuRC assembly and identify a functional role of actin in microtubule nucleation. During γ-TuRC assembly, a GCP6-stabilized core comprising GCP2-3-4-5-4-6 is expanded by stepwise recruitment, selective stabilization and conformational locking of four pre-formed GCP2-GCP3 units. Formation of the lumenal bridge specifies incorporation of the terminal GCP2-GCP3 unit and thereby leads to closure of the γ-TuRC ring in a left-handed spiral configuration. Actin incorporation into the complex is not relevant for γ-TuRC assembly and structural integrity, but determines γ-TuRC geometry and is required for efficient microtubule nucleation and mitotic chromosome alignment in vivo.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28079-0
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DOI: 10.1038/s41467-022-28079-0
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