8RX1

CryoEM structure of the gTuRC-CM1dim complex

This is a non-PDB format compatible entry.

Summary for 8RX1

• Entry DOI: 10.2210/pdb8rx1/pdb
• EMDB information: 19570
• Descriptor: Tubulin gamma-1 chain, Mitotic-spindle organizing protein 2A, Actin b, ... (10 entities in total)
• Functional Keywords: gturc, gtusc, cm1, cdk5rap2, gamma-tubulin, microtubule, alfa/beta-tubulin nucleation, cytoskeleton, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 45
• Total formula weight: 2969314.85

Authors

Llorca, O.,Serna, M.,Gonzalez-Rodriguez, N. (deposition date: 2024-02-06, release date: 2024-09-25, Last modification date: 2024-12-18)

Primary citation

Serna, M.,Zimmermann, F.,Vineethakumari, C.,Gonzalez-Rodriguez, N.,Llorca, O.,Luders, J.
CDK5RAP2 activates microtubule nucleator gamma TuRC by facilitating template formation and actin release.
Dev.Cell, 59:3175-, 2024

PubMed Abstract: To organize microtubules, cells tightly control the activity of the microtubule nucleator γ-tubulin ring complex (γTuRC). The open ring-shaped γTuRC was proposed to nucleate microtubules by a template mechanism. However, its splayed structure does not match microtubule symmetry, leaving it unclear how γTuRC becomes an efficient nucleator. Here, we identify the mechanism of γTuRC activation by CDK5RAP2 centrosomin motif 1 (CM1). Using cryoelectron microscopy (cryo-EM), we find that activation involves binding of multiple CM1 dimers to five distinct sites around the outside of the γTuRC cone, which crucially depends on regulatory modules formed by MZT2 and the N-terminal extensions of GCP2 subunits. CM1 binding promotes lateral interactions between GCP subunits to facilitate microtubule-like conformations and release of luminal actin that is integral to non-activated γTuRC. We propose a model where generation of γTuRC with an expanded conformational range, rather than perfect symmetry, is sufficient to boost nucleation activity.

PubMed: 39321809
DOI: 10.1016/j.devcel.2024.09.001

Experimental method

ELECTRON MICROSCOPY (3.57 Å)