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TitleCDK5RAP2 activates microtubule nucleator γTuRC by facilitating template formation and actin release.
Journal, issue, pagesDev Cell, Vol. 59, Issue 23, Page 3175-33188.e8, Year 2024
Publish dateDec 2, 2024
AuthorsMarina Serna / Fabian Zimmermann / Chithran Vineethakumari / Nayim Gonzalez-Rodriguez / Oscar Llorca / Jens Lüders /
PubMed AbstractTo 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 linksDev Cell / PubMed:39321809
MethodsEM (single particle)
Resolution3.57 - 8.78 Å
Structure data

EMDB-18193: Cross-linked human gTuSC oligomeric ring
Method: EM (single particle) / Resolution: 8.78 Å

EMDB-19570, PDB-8rx1:
CryoEM structure of the gTuRC-CM1dim complex
Method: EM (single particle) / Resolution: 3.57 Å

Source
  • homo sapiens (human)
  • spodoptera frugiperda (fall armyworm)
KeywordsSTRUCTURAL PROTEIN / gTuRC / gTuSC / CM1 / CDK5RAP2 / gamma-tubulin / microtubule / alfa/beta-tubulin nucleation / cytoskeleton

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