5ij9 | pdb_00005ij9
Cryo EM density of microtubule assembled from human TUBB3-D417H mutant
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. 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 PubMedThe 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. See AlsoReferences
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