5ij9 | pdb_00005ij9

Cryo EM density of microtubule assembled from human TUBB3-D417H mutant

Structural highlights

5ij9 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	GDP, GTP, MG
Related:	5ij0
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

Function

[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. [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]

Publication Abstract from PubMed

The assembly of microtubule-based cellular structures depends on regulated tubulin polymerization and directional transport. Here, we purify and characterize tubulin heterodimers that have human beta-tubulin isotype III (TUBB3), as well as heterodimers with one of two beta-tubulin mutations (D417H or R262H). Both point mutations are proximal to the kinesin-binding site and have been linked to an ocular motility disorder in humans. Compared to wild-type, microtubules with these mutations have decreased catastrophe frequencies and increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly, the D417H mutation does not alter microtubule lattice structure or Mal3 binding to growing filaments. Instead, this mutation reduces the affinity of tubulin for TOG domains and colchicine, suggesting that the distribution of tubulin heterodimer conformations is changed. Together, our findings reveal how residues on the surface of microtubules, distal from the GTP-hydrolysis site and inter-subunit contacts, can alter polymerization dynamics at the plus- and minus-ends of microtubules.

Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends.,Ti SC, Pamula MC, Howes SC, Duellberg C, Cade NI, Kleiner RE, Forth S, Surrey T, Nogales E, Kapoor TM Dev Cell. 2016 Apr 4;37(1):72-84. doi: 10.1016/j.devcel.2016.03.003. PMID:27046833^[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:https://dx.doi.org/10.1016/j.cell.2009.12.011
↑ Ti SC, Pamula MC, Howes SC, Duellberg C, Cade NI, Kleiner RE, Forth S, Surrey T, Nogales E, Kapoor TM. Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends. Dev Cell. 2016 Apr 4;37(1):72-84. doi: 10.1016/j.devcel.2016.03.003. PMID:27046833 doi:https://dx.doi.org/10.1016/j.devcel.2016.03.003

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OCA

[1] 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:https://dx.doi.org/10.1016/j.cell.2009.12.011

[2] Ti SC, Pamula MC, Howes SC, Duellberg C, Cade NI, Kleiner RE, Forth S, Surrey T, Nogales E, Kapoor TM. Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends. Dev Cell. 2016 Apr 4;37(1):72-84. doi: 10.1016/j.devcel.2016.03.003. PMID:27046833 doi:https://dx.doi.org/10.1016/j.devcel.2016.03.003

[1]

[2]

5ij9 | pdb_00005ij9

Cryo EM density of microtubule assembled from human TUBB3-D417H mutant

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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