Gadd45 beta forms a homodimeric complex that binds tightly to MKK7(483 views) Tornatore L, Marasco D, Dathan N, Vitale RM, Benedetti E, Papa S, Franzoso G, Ruvo M, Monti SM
Keywords: Dimerization, Gadd45b, Mkk7, Oligomerization, Protein-Protein Interaction, Growth Arrest And Dna Damage Inducible Protein 45, Mitogen Activated Protein Kinase Kinase 7, Article, Biotinylation, Circular Dichroism, Enzyme Isolation, Gel Electrophoresis, Peptide Synthesis, Priority Journal, Protein Binding, Protein Expression, Protein Purification, Amino Acid Sequence, Antigens, Differentiation, Chromatography, Humans, Map Kinase Kinase 7, Molecular Sequence Data, Protein Conformation, Protein Interaction Mapping, Chemistry, Genetics,
Affiliations: *** IBB - CNR ***
Istituto di Biostrutture e Bioimmagini (IBB), CNR, via Mezzocannone, 16, 80134 Napoli, Italy
Dipartimento delle Scienze Biologiche, via Mezzocannone, 16, 80134 Napoli, Italy
Istituto di Chimica Biomolecolare (ICB), CNR, Via Campi Flegrei, 34, 80078 Pozzuoli, NA, Italy
Department of Immunology at Hammersmith, Division of Investigative Science, Imperial College, London, Du Cane Road, London, W12 ONN, United Kingdom
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Gadd45 beta forms a homodimeric complex that binds tightly to MKK7
Gadd45 alpha, beta, and gamma 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, Gadd45 beta has been indicated as a major player in the endogenous NF-kappa B-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 Gadd45 beta and the Gadd45 beta-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 Gadd45 beta. Here, we provide further evidence that Gadd45 beta is a prevailingly alpha-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 Gadd45 alpha. 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-Gadd45 beta: Gadd45 beta -MKK7 tetrameric unit whose complexity could be further increased by the dimeric nature of the isolated MKK7
Gadd45 beta forms a homodimeric complex that binds tightly to MKK7