Ask about this productRelated genes to: TBCD Blocking Peptide
- Gene:
- TBCD NIH gene
- Name:
- tubulin folding cofactor D
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-07-31
- Date modifiied:
- 2016-12-12
Related products to: TBCD Blocking Peptide
Related articles to: TBCD Blocking Peptide
- Microtubules polymerize from cytoplasmic pools of soluble αβ-tubulin heterodimers that support diverse cellular functions. The tubulin cofactors, TBCC, TBCD, and TBCE and the Arl2 GTPase, form TBC-DEG assemblies that regulate the assembly of α- and β-tubulin into heterodimers and their disassembly, yet their underlying mechanisms remain incompletely understood. Here, we reconstitute the human TBC-DE and TBC-DEG assemblies from eukaryotic cells copurified with monomeric β-tubulin intermediates and determine their cryo-EM structures. The structures reveal that TBC-DEG disassembles αβ-tubulin by releasing α-tubulin through a lever arm-like rotation in TBCE coupled to major conformational change in Arl2 upon its nucleotide release, while TBCD tightly holds β-tubulin. TBCD dissociates α-tubulin by refolding the β-tubulin H10-S8 loop at its intradimer interface. The TBC-DEG-β-tubulin or TBC-DE-β-tubulin assemblies undergo extensive back-to-back dimerization mediated by β-β-tubulin homodimers, formed through their dissociated H8 helices at unoccupied intradimer interfaces. Structural comparisons demonstrate that TBCE's mechanical rotation, driven by the Arl2 GTPase cycle, either delivers α-tubulin or removes it from beneath the TBCD-bound β-tubulin and is directionally regulated by TBCC stabilizing αβ-tubulin interfaces. Our findings suggest that TBC-DEG/TBCC catalyzing heterodimerization of α-tubulin with β-tubulin may have evolved to counteract β-tubulin's intrinsic tendency to form off-pathway toxic homodimers through its exposed α-tubulin-binding intradimer interface. - Source: PubMed
Publication date: 2026/05/08
Taheri AryanAshaduzzaman MdGill VishvEskin Julian AAl-Bassam Jawdat - Tubulin-folding cofactor E (TBCE) plays a central role in tubulin heterodimer formation and disaggregation. Both TBCE biallelic and monoallelic pathogenic variants have been associated with human diseases involving endocrine and/or neurologic system. This study aimed to expand current knowledge on the neurodegenerative phenotype associated with TBCE variants, and to explore possible genotype-phenotype correlations. - Source: PubMed
Publication date: 2026/03/04
Sartorelli JacopoSgobbi PauloBattini RobertaSchifino MariapaolaTrovato RosannaCompagnucci ClaudiaLauri AntonellaTartaglia MarcoSferra AntonellaD'Amico AdeleDiodato DariaBertini EnricoNicita Francesco - Microtubules polymerize from cytoplasmic pools of soluble αβ-tubulin heterodimers that support diverse cellular functions. The tubulin cofactors, TBCC, TBCD, TBCE, and the Arl2 GTPase, form TBC-DEG assemblies that regulate αβ-tubulin assembly and disassembly from α- and β-tubulins, yet their underlying mechanisms remain incompletely understood. Here, we reconstitute the human TBC-DE and TBC-DEG assemblies from eukaryotic cells co-purified with monomeric β-tubulin intermediates and determine their cryo-EM structures. The structures reveal that TBC-DEG disassembles αβ-tubulin by releasing α-tubulin through a lever-arm-like rotation in TBCE coupled to major conformational change in Arl2 upon its nucleotide release, while TBCD tightly holds β-tubulin. TBCD dissociates α-tubulin by refolding the β-tubulin H10-S8 loop at its intradimer interface. The TBC-DEG-β-tubulin or TBC-DE-β-tubulin assemblies undergo extensive back-to-back dimerization mediated by β-β-tubulin homodimers, formed through their dissociated H8 helices at unoccupied intradimer interfaces. Structural comparisons demonstrate that the TBCE mechanical rotation, driven by the Arl2 GTPase cycle, either delivers α-tubulin or removes it from beneath the TBCD-bound β-tubulin and is directionally regulated by TBCC stabilizing αβ-tubulin interfaces. Our findings suggest that TBC-DEG/TBCC catalyzing heterodimerization of α-tubulin with β-tubulin may have evolved to counteract the β-tubulin intrinsic tendency to form off-pathway toxic homodimers through its exposed α-tubulin-binding intradimer interface. - Source: PubMed
Publication date: 2025/12/31
Taheri AryanAshaduzzaman MdGill VishvAl-Bassam Jawdat - Reis-Bücklers corneal dystrophy (RBCD; Mendelian Inheritance in Man 602082) and Thiel-Behnke corneal dystrophy (TBCD; Mendelian Inheritance in Man 608470) are clinically similar corneal dystrophies affecting Bowman's layer, caused by the TGFBI variants p.(Arg124Leu) and p.(Arg555Gln), respectively. Yet their distinct clinical courses complicate therapeutic decisions. This study aimed to compare the clinical course and surgical outcomes of genetically confirmed RBCD and TBCD. - Source: PubMed
Publication date: 2025/12/12
Mahoun ZacharyValleix SophieBourges Jean-Louis - Microtubule polarity and dynamic polymerization arise from the self-association properties of the αβ-tubulin heterodimer. For decades, it has remained unclear how the tubulin cofactors TBCD, TBCE, TBCC, and the Arl2 GTPase mediate the biogenesis of αβ-tubulin from individual α- and β-tubulins. Here, we use cryo-electron microscopy to determine structures of tubulin cofactors bound to αβ-tubulin. TBCD, TBCE, and Arl2 form a heterotrimeric cage-like assembly, we term TBC-DEG, around the αβ-tubulin heterodimer. The TBC-DEG-αβ-tubulin structures show that TBC-DEG wraps around β-tubulin while TBCE extends along α-tubulin. The TBC-DEG/TBCC-αβ-tubulin structures reveal that TBCC forms multi-domain interactions with Arl2 and TBCD to engage the αβ-tubulin intradimer-interface, promoting TBCE rotation while TBCD holds β-tubulin. TBCC engages the GTP-bound Arl2, multiple sites of TBCD, and the native αβ-tubulin intradimer interface near the α-tubulin N-site GTP. Together, these structures uncover transition states for αβ-tubulin biogenesis and degradation, suggesting a vise-like, GTP-hydrolysis-dependent mechanism in which TBCC binding to TBC-DEG modulates αβ-tubulin interfaces. Our studies provide structural evidence that tubulin cofactors act as enzymatic regulators that assemble the invariant αβ-tubulin architecture. By catalyzing α- and β-tubulin biogenesis and degradation, the TBC-DEG and TBCC assemblies regulate the polymerization competency of αβ-tubulin for microtubule formation. - Source: PubMed
Publication date: 2025/12/29
Taheri AryanWang ZhoaqianSingal BhartiGuo FeiAl-Bassam Jawdat