| Structural highlights
Disease
[TBB3_HUMAN] Congenital fibrosis of extraocular muscles;Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. [TBA1A_HUMAN] Lissencephaly due to TUBA1A mutation. The disease is caused by mutations affecting the gene represented in this entry.
Function
[TBB3_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. TUBB3 plays a critical role in proper axon guidance and mantainance.[1] [TBA1A_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
Microtubules are polymers that cycle stochastically between polymerization and depolymerization i.e., they exhibit 'dynamic instability'. This behavior is crucial for cell division, motility and differentiation. While studies in the last decade have made fundamental breakthroughs in our understanding of how cellular effectors modulate microtubule dynamics, analysis of the relationship between tubulin sequence, structure and dynamics has been held back by a lack of dynamics measurements with and structural characterization of homogenous, isotypically pure, engineered tubulin. Here we report for the first time the cryo-EM structure and in vitro dynamics parameters of recombinant isotypically pure human tubulin. alpha1A/betaIII is a purely neuronal tubulin isoform. The 4.2 A structure of unmodified human alpha1A/betaIII microtubules shows overall similarity to that of heterogeneous brain microtubules, but is distinguished by subtle differences at polymerization interfaces, which are hotspots for sequence divergence between tubulin isoforms. In vitro dynamics assays show that, like mosaic brain microtubules, recombinant homogenous microtubules undergo dynamic instability but they polymerize slower and catastrophe less frequently. Interestingly, we find that epitaxial growth of alpha1A/betaIII microtubules from heterogeneous brain seeds is inefficient, but can be fully rescued by incorporating as little as 5% of brain tubulin into the homogenous alpha1A/betaIII lattice. Our study establishes a system to examine the structure and dynamics of mammalian microtubules with well-defined tubulin species and is a first and necessary step towards uncovering how tubulin genetic and chemical diversity is exploited to modulate intrinsic microtubule dynamics.
Structure and Dynamics of Single-isoform Recombinant Neuronal Human Tubulin.,Vemu A, Atherton J, Spector JO, Szyk A, Moores CA, Roll-Mecak A J Biol Chem. 2016 Apr 25. pii: jbc.C116.731133. PMID:27129203[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tischfield MA, Baris HN, Wu C, Rudolph G, Van Maldergem L, He W, Chan WM, Andrews C, Demer JL, Robertson RL, Mackey DA, Ruddle JB, Bird TD, Gottlob I, Pieh C, Traboulsi EI, Pomeroy SL, Hunter DG, Soul JS, Newlin A, Sabol LJ, Doherty EJ, de Uzcategui CE, de Uzcategui N, Collins ML, Sener EC, Wabbels B, Hellebrand H, Meitinger T, de Berardinis T, Magli A, Schiavi C, Pastore-Trossello M, Koc F, Wong AM, Levin AV, Geraghty MT, Descartes M, Flaherty M, Jamieson RV, Moller HU, Meuthen I, Callen DF, Kerwin J, Lindsay S, Meindl A, Gupta ML Jr, Pellman D, Engle EC. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell. 2010 Jan 8;140(1):74-87. doi: 10.1016/j.cell.2009.12.011. PMID:20074521 doi:http://dx.doi.org/10.1016/j.cell.2009.12.011
- ↑ Vemu A, Atherton J, Spector JO, Szyk A, Moores CA, Roll-Mecak A. Structure and Dynamics of Single-isoform Recombinant Neuronal Human Tubulin. J Biol Chem. 2016 Apr 25. pii: jbc.C116.731133. PMID:27129203 doi:http://dx.doi.org/10.1074/jbc.C116.731133
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