The HMGB1 acidic tail regulates HMGB1 DNA binding specificity by a unique mechanism.
HMGB1 is a conserved chromosomal protein composed of two DNA-binding domains and an acidic C-terminal tail. There were evidences suggesting that the C-terminal tail contributed to the DNA binding specificity of the N-terminal DNA-binding domains. However, the mechanism underlining this observation is largely unknown. Our data first confirmed the previous study with NMR that showed a direct interaction between HMGB1's C-terminal tail and its N-terminal domains. We further demonstrated that this interaction can be competed more efficiently by a DNA with four-way junction structure than by a linear double-stranded DNA. Mutations within the N-terminal region, that disrupt its binding to the C-terminal tail, abolished HMGB1's ability to distinguish the linear DNA and the four-way junction DNA. Those data suggested a unique mechanism designed by nature that utilizes a protein's negatively charged C-terminal tail to enhance its DNA-binding domain's specificity to certain structured DNAs.
Wang
Qiyu
Q
National Laboratory of Biomacromolecules, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Room 1407, 15 Datun Road, Chaoyang District, Beijing 100101, PR China.
Zeng
Minghui
M
Wang
Wei
W
Tang
Jie
J
D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure; D024243:HMGB1 Protein / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D024243:HMGB1 Protein; D004247:DNA