9M1J

Cryo-EM structure of the TBC-DE-Arl2-beta-tubulin complex

Summary for 9M1J

• Entry DOI: 10.2210/pdb9m1j/pdb
• EMDB information: 63573
• Descriptor: Tubulin-specific chaperone D, Tubulin-specific chaperone E, ADP-ribosylation factor-like protein 2, ... (6 entities in total)
• Functional Keywords: chaperone, complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 245285.98

Authors

Seong, Y.J.,Kim, H.M.,Byun, K.M.,Park, Y.W.,Roh, S.H. (deposition date: 2025-02-26, release date: 2025-10-22, Last modification date: 2025-11-12)

Primary citation

Seong, Y.,Kim, H.,Byun, K.,Park, Y.W.,Roh, S.H.
Structural dissection of alpha beta-tubulin heterodimer assembly and disassembly by human tubulin-specific chaperones.
Science, 390:eady2708-eady2708, 2025

PubMed Abstract: Microtubule assembly requires a set of chaperones known as tubulin-binding cofactors (TBCs). We used cryo-electron microscopy to visualize how human TBCD, TBCE, TBCC, and guanosine triphosphatase (GTPase) Arl2 mediate αβ-tubulin assembly and disassembly. We captured multiple conformational states, revealing how TBCs orchestrate tubulin heterodimer biogenesis. TBCD stabilizes monomeric β-tubulin and scaffolds the other cofactors. Guanosine triphosphate (GTP) binding to Arl2 induces conformational changes that toggle the complex between assembly and disassembly. TBCD and TBCE guide α- and β-tubulin into a partially assembled interface, and TBCC, acting as a molecular clamp, completes the heterodimer. TBCD also functions as a GTPase activating protein for β-tubulin. β-tubulin GTP hydrolysis is coupled to Arl2's GTPase activity, establishing a checkpoint that ensures that only fully matured heterodimers proceed. These findings provide a structural framework for tubulin heterodimer biogenesis and recycling, supporting cytoskeletal proteostasis.

PubMed: 41166473
DOI: 10.1126/science.ady2708

Experimental method

ELECTRON MICROSCOPY (2.14 Å)