| Structural highlights
Disease
[TBB2B_HUMAN] Congenital fibrosis of extraocular muscles;Polymicrogyria due to TUBB2B mutation. The disease is caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry. Defects in TUBB2B may be involved in cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ).[1]
Function
[TBB2B_HUMAN] Tubulin is the major constituent of microtubules (PubMed:23001566, PubMed:28013290, PubMed:26732629). It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity). Plays a critical role in proper axon guidance in both central and peripheral axon tracts (PubMed:23001566). Implicated in neuronal migration (PubMed:19465910).[2] [3] [4] [5] [TBA1B_HUMAN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Publication Abstract from PubMed
Cell biological studies have shown that protofilament number, a fundamental feature of microtubules, can correlate with the expression of different tubulin isotypes. However, it is not known if tubulin isotypes directly control this basic microtubule property. Here, we report high-resolution cryo-EM reconstructions (3.5-3.65 A) of purified human alpha1B/beta3 and alpha1B/beta2B microtubules and find that the beta-tubulin isotype can determine protofilament number. Comparisons of atomic models of 13- and 14-protofilament microtubules reveal how tubulin subunit plasticity, manifested in "accordion-like" distributed structural changes, can accommodate distinct lattice organizations. Furthermore, compared to alpha1B/beta3 microtubules, alpha1B/beta2B filaments are more stable to passive disassembly and against depolymerization by MCAK or chTOG, microtubule-associated proteins with distinct mechanisms of action. Mixing tubulin isotypes in different proportions results in microtubules with protofilament numbers and stabilities intermediate to those of isotypically pure filaments. Together, our findings indicate that microtubule protofilament number and stability can be controlled through beta-tubulin isotype composition.
Human beta-Tubulin Isotypes Can Regulate Microtubule Protofilament Number and Stability.,Ti SC, Alushin GM, Kapoor TM Dev Cell. 2018 Sep 18. pii: S1534-5807(18)30684-1. doi:, 10.1016/j.devcel.2018.08.014. PMID:30245156[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Breuss MW, Nguyen T, Srivatsan A, Leca I, Tian G, Fritz T, Hansen AH, Musaev D, McEvoy-Venneri J, James KN, Rosti RO, Scott E, Tan U, Kolodner RD, Cowan NJ, Keays DA, Gleeson JG. Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability. Hum Mol Genet. 2017 Jan 15;26(2):258-269. doi: 10.1093/hmg/ddw383. PMID:28013290 doi:http://dx.doi.org/10.1093/hmg/ddw383
- ↑ Jaglin XH, Poirier K, Saillour Y, Buhler E, Tian G, Bahi-Buisson N, Fallet-Bianco C, Phan-Dinh-Tuy F, Kong XP, Bomont P, Castelnau-Ptakhine L, Odent S, Loget P, Kossorotoff M, Snoeck I, Plessis G, Parent P, Beldjord C, Cardoso C, Represa A, Flint J, Keays DA, Cowan NJ, Chelly J. Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria. Nat Genet. 2009 Jun;41(6):746-52. doi: 10.1038/ng.380. Epub 2009 May 24. PMID:19465910 doi:http://dx.doi.org/10.1038/ng.380
- ↑ Cederquist GY, Luchniak A, Tischfield MA, Peeva M, Song Y, Menezes MP, Chan WM, Andrews C, Chew S, Jamieson RV, Gomes L, Flaherty M, Grant PE, Gupta ML Jr, Engle EC. An inherited TUBB2B mutation alters a kinesin-binding site and causes polymicrogyria, CFEOM and axon dysinnervation. Hum Mol Genet. 2012 Dec 15;21(26):5484-99. doi: 10.1093/hmg/dds393. Epub 2012 Sep, 21. PMID:23001566 doi:http://dx.doi.org/10.1093/hmg/dds393
- ↑ Laquerriere A, Gonzales M, Saillour Y, Cavallin M, Joye N, Quelin C, Bidat L, Dommergues M, Plessis G, Encha-Razavi F, Chelly J, Bahi-Buisson N, Poirier K. De novo TUBB2B mutation causes fetal akinesia deformation sequence with microlissencephaly: An unusual presentation of tubulinopathy. Eur J Med Genet. 2016 Apr;59(4):249-56. doi: 10.1016/j.ejmg.2015.12.007. Epub, 2015 Dec 28. PMID:26732629 doi:http://dx.doi.org/10.1016/j.ejmg.2015.12.007
- ↑ Breuss MW, Nguyen T, Srivatsan A, Leca I, Tian G, Fritz T, Hansen AH, Musaev D, McEvoy-Venneri J, James KN, Rosti RO, Scott E, Tan U, Kolodner RD, Cowan NJ, Keays DA, Gleeson JG. Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability. Hum Mol Genet. 2017 Jan 15;26(2):258-269. doi: 10.1093/hmg/ddw383. PMID:28013290 doi:http://dx.doi.org/10.1093/hmg/ddw383
- ↑ Ti SC, Alushin GM, Kapoor TM. Human beta-Tubulin Isotypes Can Regulate Microtubule Protofilament Number and Stability. Dev Cell. 2018 Sep 18. pii: S1534-5807(18)30684-1. doi:, 10.1016/j.devcel.2018.08.014. PMID:30245156 doi:http://dx.doi.org/10.1016/j.devcel.2018.08.014
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