Crystal structure of human Gadd45γ corrected reveals an active dimer.
10.1007/s13238-011-1090-6
- Author:
Wenzheng ZHANG
1
;
Sheng FU
;
Xuefeng LIU
;
Xuelian ZHAO
;
Wenchi ZHANG
;
Wei PENG
;
Congying WU
;
Yuanyuan LI
;
Xuemei LI
;
Mark BARTLAM
;
Zong-Hao ZENG
;
Qimin ZHAN
;
Zihe RAO
Author Information
1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
- Publication Type:Journal Article
- MeSH:
Amino Acid Motifs;
Animals;
Apoptosis;
radiation effects;
CDC2 Protein Kinase;
Cell Cycle;
Cell Survival;
Crystallography, X-Ray;
Cyclin B;
metabolism;
Cyclin-Dependent Kinase Inhibitor p21;
metabolism;
Cyclin-Dependent Kinases;
HeLa Cells;
Humans;
Intracellular Signaling Peptides and Proteins;
chemistry;
genetics;
metabolism;
Mice;
Mutagenesis, Site-Directed;
Mutation, Missense;
Proliferating Cell Nuclear Antigen;
metabolism;
Protein Binding;
Protein Interaction Domains and Motifs;
Protein Multimerization;
Protein Structure, Quaternary;
Ultraviolet Rays
- From:
Protein & Cell
2011;2(10):814-826
- CountryChina
- Language:English
-
Abstract:
The human Gadd45 protein family plays critical roles in DNA repair, negative growth control, genomic stability, cell cycle checkpoints and apoptosis. Here we report the crystal structure of human Gadd45γ [corrected], revealing a unique dimer formed via a bundle of four parallel helices, involving the most conserved residues among the Gadd45 isoforms. Mutational analysis of human Gadd45γ [corrected] identified a conserved, highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen (PCNA), p21 and cdc2, suggesting that the parallel dimer is the active form for the interaction. Cellular assays indicate that: (1) dimerization of Gadd45γ [corrected] is necessary for apoptosis as well as growth inhibition, and that cell growth inhibition is caused by both cell cycle arrest and apoptosis; (2) a conserved and highly acidic patch on the dimer surface, including the important residues Glu87 and Asp89, is a putative interface for binding proteins related to the cell cycle, DNA repair and apoptosis. These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.
