A structural model for the autoinhibition of the γ-TuRC-activating CM1 domain

Abstract

Microtubule nucleation by γ-tubulin ring complexes (γ-TuRCs) must be spatiotemporally controlled to avoid major cell division errors. γ-TuRCs are activated by the centrosome-specific binding of a highly conserved Centrosomin Motif 1 (CM1) domain, but how binding is prevented in the cytosol remains unclear. We provide the first structural explanation for CM1 autoinhibition, revealing that stable intramolecular interactions mediate cooperative folding to block γ-TuRC binding interfaces. Using various structural approaches, we show that the CM1 forms a conserved dimeric coiled-coil hairpin that sequesters a key phenylalanine residue essential for γ-TuRC binding. This appears sufficient for autoinhibition in humans, but in flies autoinhibition requires the association of an upstream “CM1 autoinhibition” (CAI) domain, which forms a 4-helix dimer that covers the opposite phenylalanine residue of the hairpin dimer. Collectively, the data provide the first structural model for CM1 autoinhibition and reveal evolutionary differences across species.

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BibTeX RIS

BibTeX

@article{elfarkouchi2026structural,
  title = {{A structural model for the autoinhibition of the γ-TuRC-activating CM1 domain}},
  author = {Abir Elfarkouchi and Arthur Vitard and Léa Mammri and Sébastien Brier and Lola Tanneur and Cécile Hu and Aurélien Thureau and Nicolas Joly and Françoise Ochsenbein and Paul T Conduit},
  journal = {Journal of Cell Biology},
  year = {2026},
  month = sep,
  doi = {10.1083/jcb.202605160},
  url = {https://hal.science/hal-05756468v1},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - A structural model for the autoinhibition of the γ-TuRC-activating CM1 domain
AU  - Abir Elfarkouchi
AU  - Arthur Vitard
AU  - Léa Mammri
AU  - Sébastien Brier
AU  - Lola Tanneur
AU  - Cécile Hu
AU  - Aurélien Thureau
AU  - Nicolas Joly
AU  - Françoise Ochsenbein
AU  - Paul T Conduit
PY  - 2026
DA  - 2026/09/30
JO  - Journal of Cell Biology
DO  - 10.1083/jcb.202605160
UR  - https://hal.science/hal-05756468v1
AB  - Microtubule nucleation by γ-tubulin ring complexes (γ-TuRCs) must be spatiotemporally controlled to avoid major cell division errors. γ-TuRCs are activated by the centrosome-specific binding of a highly conserved Centrosomin Motif 1 (CM1) domain, but how binding is prevented in the cytosol remains unclear. We provide the first structural explanation for CM1 autoinhibition, revealing that stable intramolecular interactions mediate cooperative folding to block γ-TuRC binding interfaces. Using various structural approaches, we show that the CM1 forms a conserved dimeric coiled-coil hairpin that sequesters a key phenylalanine residue essential for γ-TuRC binding. This appears sufficient for autoinhibition in humans, but in flies autoinhibition requires the association of an upstream “CM1 autoinhibition” (CAI) domain, which forms a 4-helix dimer that covers the opposite phenylalanine residue of the hairpin dimer. Collectively, the data provide the first structural model for CM1 autoinhibition and reveal evolutionary differences across species.
SN  - 0021-9525
SN  - 1540-8140
ER  -

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