4ICV

Ubiquitin-like domain of human tubulin folding cofactor E - crystal form B

Summary for 4ICV

• Entry DOI: 10.2210/pdb4icv/pdb
• Related: 4ICU
• Descriptor: Tubulin-specific chaperone E, PRASEODYMIUM ION (3 entities in total)
• Functional Keywords: ubiquitin-like domain, tubulin folding cofactor, alpha tubulin, tubulin folding cofactor b, chaperone
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q15813
• Total number of polymer chains: 1
• Total formula weight: 10242.25

Authors

Janowski, R.,Boutin, M.,Zabala, J.C.,Coll, M. (deposition date: 2012-12-11, release date: 2014-06-18, Last modification date: 2024-02-28)

Primary citation

Serna, M.,Carranza, G.,Martin-Benito, J.,Janowski, R.,Canals, A.,Coll, M.,Zabala, J.C.,Valpuesta, J.M.
The structure of the complex between alpha-tubulin, TBCE and TBCB reveals a tubulin dimer dissociation mechanism.
J.Cell.Sci., 128:1824-1834, 2015

PubMed Abstract: Tubulin proteostasis is regulated by a group of molecular chaperones termed tubulin cofactors (TBC). Whereas tubulin heterodimer formation is well-characterized biochemically, its dissociation pathway is not clearly understood. Here, we carried out biochemical assays to dissect the role of the human TBCE and TBCB chaperones in α-tubulin-β-tubulin dissociation. We used electron microscopy and image processing to determine the three-dimensional structure of the human TBCE, TBCB and α-tubulin (αEB) complex, which is formed upon α-tubulin-β-tubulin heterodimer dissociation by the two chaperones. Docking the atomic structures of domains of these proteins, including the TBCE UBL domain, as we determined by X-ray crystallography, allowed description of the molecular architecture of the αEB complex. We found that heterodimer dissociation is an energy-independent process that takes place through a disruption of the α-tubulin-β-tubulin interface that is caused by a steric interaction between β-tubulin and the TBCE cytoskeleton-associated protein glycine-rich (CAP-Gly) and leucine-rich repeat (LRR) domains. The protruding arrangement of chaperone ubiquitin-like (UBL) domains in the αEB complex suggests that there is a direct interaction of this complex with the proteasome, thus mediating α-tubulin degradation.

PubMed: 25908846
DOI: 10.1242/jcs.167387

Experimental method

X-RAY DIFFRACTION (1.45 Å)