Gadd45β forms a Homodimeric Complex that Binds Tightly to MKK7

Gadd45α, β, and γ proteins, also known as growth arrest and DNA damage-inducible factors, have a number of cellular functions, including cell-cycle regulation and propagation of signals produced by a variety of cellular stimuli, maintaining genomic stability and apoptosis. Furthermore, Gadd45β has b...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular biology 2008-04, Vol.378 (1), p.97-111
Main Authors: Tornatore, Laura, Marasco, Daniela, Dathan, Nina, Vitale, Rosa Maria, Benedetti, Ettore, Papa, Salvatore, Franzoso, Guido, Ruvo, Menotti, Monti, Simona Maria
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antigens, Differentiation - chemistry
Antigens, Differentiation - genetics
Antigens, Differentiation - isolation & purification
Chromatography, Gel
Circular Dichroism
Dimerization
Gadd45b
Humans
MAP Kinase Kinase 7 - chemistry
MAP Kinase Kinase 7 - genetics
MAP Kinase Kinase 7 - isolation & purification
MKK7
Molecular Sequence Data
oligomerization
Protein Conformation
Protein Interaction Mapping
protein-protein interaction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Gadd45α, β, and γ proteins, also known as growth arrest and DNA damage-inducible factors, have a number of cellular functions, including cell-cycle regulation and propagation of signals produced by a variety of cellular stimuli, maintaining genomic stability and apoptosis. Furthermore, Gadd45β has been indicated as a major player in the endogenous NF-κB-mediated resistance to apoptosis in a variety of cell lines. In fibroblasts this mechanism involves the inactivation of MKK7, the upstream activator of JNK, by direct binding within the kinase ATP pocket. On the basis of a number of experimental data, the structures of Gadd45β and the Gadd45β-MKK7 complex have been predicted recently and data show that interactions are mediated by acidic loops 1 and 2, and helices 3 and 4 of Gadd45β. Here, we provide further evidence that Gadd45β is a prevailingly α-helical protein and that in solution it is able to form non covalent dimers but not higher-order oligomers, in contrast to what has been reported for the homologous Gadd45α. We show that the contact region between the two monomers is comprised of the predicted helix 1 (residues Q17–Q33) and helix 5 (residues K131–R146) of the protein, which appear to be antiparallel and to form a large dimerisation surface not involved in MKK7 recognition. The results suggest the occurrence of a large complex containing at least an MKK7-Gadd45β:Gadd45β-MKK7 tetrameric unit whose complexity could be further increased by the dimeric nature of the isolated MKK7.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2008.01.074