7qj6 | pdb_00007qj6

Structure of recombinant human gamma-Tubulin Ring Complex 10-spoked assembly intermediate (spokes 3-12, substoichiometric spokes 13-14)

Structural highlights

7qj6 is a 31 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 7.8Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ACTB_HUMAN Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:607371. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.^[1] Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:243310. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.^[2]

Function

ACTB_HUMAN Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Publication Abstract from PubMed

The gamma-tubulin ring complex (gamma-TuRC) is the principal microtubule nucleation template in vertebrates. Recent cryo-EM reconstructions visualized the intricate quaternary structure of the gamma-TuRC, containing more than thirty subunits, raising fundamental questions about gamma-TuRC assembly and the role of actin as an integral part of the complex. Here, we reveal the structural mechanism underlying modular gamma-TuRC assembly and identify a functional role of actin in microtubule nucleation. During gamma-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 gamma-TuRC ring in a left-handed spiral configuration. Actin incorporation into the complex is not relevant for gamma-TuRC assembly and structural integrity, but determines gamma-TuRC geometry and is required for efficient microtubule nucleation and mitotic chromosome alignment in vivo.

Modular assembly of the principal microtubule nucleator gamma-TuRC.,Wurtz M, Zupa E, Atorino ES, Neuner A, Bohler A, Rahadian AS, Vermeulen BJA, Tonon G, Eustermann S, Schiebel E, Pfeffer S Nat Commun. 2022 Jan 25;13(1):473. doi: 10.1038/s41467-022-28079-0. PMID:35078983^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst CA, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH. A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. Am J Hum Genet. 2006 Jun;78(6):947-60. Epub 2006 Apr 21. PMID:16685646 doi:S0002-9297(07)63917-2
↑ Riviere JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet. 2012 Feb 26;44(4):440-4, S1-2. doi: 10.1038/ng.1091. PMID:22366783 doi:10.1038/ng.1091
↑ Würtz M, Zupa E, Atorino ES, Neuner A, Böhler A, Rahadian AS, Vermeulen BJA, Tonon G, Eustermann S, Schiebel E, Pfeffer S. Modular assembly of the principal microtubule nucleator γ-TuRC. Nat Commun. 2022 Jan 25;13(1):473. PMID:35078983 doi:10.1038/s41467-022-28079-0

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OCA

[1] Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst CA, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH. A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. Am J Hum Genet. 2006 Jun;78(6):947-60. Epub 2006 Apr 21. PMID:16685646 doi:S0002-9297(07)63917-2

[2] Riviere JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet. 2012 Feb 26;44(4):440-4, S1-2. doi: 10.1038/ng.1091. PMID:22366783 doi:10.1038/ng.1091

[3] Würtz M, Zupa E, Atorino ES, Neuner A, Böhler A, Rahadian AS, Vermeulen BJA, Tonon G, Eustermann S, Schiebel E, Pfeffer S. Modular assembly of the principal microtubule nucleator γ-TuRC. Nat Commun. 2022 Jan 25;13(1):473. PMID:35078983 doi:10.1038/s41467-022-28079-0

[1]

[2]

[3]

7qj6 | pdb_00007qj6

Structure of recombinant human gamma-Tubulin Ring Complex 10-spoked assembly intermediate (spokes 3-12, substoichiometric spokes 13-14)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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