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| Title | CDK5RAP2 activates microtubule nucleator γTuRC by facilitating template formation and actin release. |
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| Journal, issue, pages | Dev Cell, Vol. 59, Issue 23, Page 3175-33188.e8, Year 2024 |
| Publish date | Dec 2, 2024 |
Authors | Marina Serna / Fabian Zimmermann / Chithran Vineethakumari / Nayim Gonzalez-Rodriguez / Oscar Llorca / Jens Lüders / ![]() |
| 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 ...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. |
External links | Dev Cell / PubMed:39321809 |
| Methods | EM (single particle) |
| Resolution | 3.57 - 8.78 Å |
| Structure data | ![]() EMDB-18193: Cross-linked human gTuSC oligomeric ring EMDB-19570, PDB-8rx1: |
| Source |
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Keywords | STRUCTURAL PROTEIN / gTuRC / gTuSC / CM1 / CDK5RAP2 / gamma-tubulin / microtubule / alfa/beta-tubulin nucleation / cytoskeleton |
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