The solution structure of the N-terminal domain of human tubulin binding cofactor C reveals a platform for tubulin interaction

Human Tubulin Binding Cofactor C (TBCC) is a post-chaperonin involved in the folding and assembly of α- and β-tubulin monomers leading to the release of productive tubulin heterodimers ready to polymerize into microtubules. In this process it collaborates with other cofactors (TBC's A, B, D, an...

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Bibliographic Details
Published in:PloS one 2011-10, Vol.6 (10), p.e25912-e25912
Main Authors: Garcia-Mayoral, Ma Flor, Castaño, Raquel, Fanarraga, Monica L, Zabala, Juan Carlos, Rico, Manuel, Bruix, Marta
Format: Article
Language:English
Subjects:
Binding
Biology
Centrosome - metabolism
Chemistry
Cofactors
Handedness
HeLa Cells
Helices
Humans
Mammals
Membrane proteins
Microtubules
Models, Molecular
Molecular Chaperones - chemistry
Molecular Chaperones - metabolism
Monomers
N-Terminus
NMR
Nuclear magnetic resonance
Nuclear Magnetic Resonance, Biomolecular
Physics
Protein Binding
Protein Multimerization
Protein Structure, Quaternary
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins
RNA polymerase
Solutions
Spectrin
Spindles
Studies
Topology
Tubulin
Tubulin - chemistry
Tubulin - metabolism
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Summary:Human Tubulin Binding Cofactor C (TBCC) is a post-chaperonin involved in the folding and assembly of α- and β-tubulin monomers leading to the release of productive tubulin heterodimers ready to polymerize into microtubules. In this process it collaborates with other cofactors (TBC's A, B, D, and E) and forms a supercomplex with TBCD, β-tubulin, TBCE and α-tubulin. Here, we demonstrate that TBCC depletion results in multipolar spindles and mitotic failure. Accordingly, TBCC is found at the centrosome and is implicated in bipolar spindle formation. We also determine by NMR the structure of the N-terminal domain of TBCC. The TBCC N-terminal domain adopts a spectrin-like fold topology composed of a left-handed 3-stranded α-helix bundle. Remarkably, the 30-residue N-terminal segment of the TBCC N-terminal domain is flexible and disordered in solution. This unstructured region is involved in the interaction with tubulin. Our data lead us to propose a testable model for TBCC N-terminal domain/tubulin recognition in which the highly charged N-terminus as well as residues from the three helices and the loops interact with the acidic hypervariable regions of tubulin monomers.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0025912