The anti-inflammatory activity of HMGB1 A box is enhanced when fused with C-terminal acidic tail.
HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence (Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box.
Gong
Wei
W
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
Zheng
Yingru
Y
Chao
Fan
F
Li
Yuan
Y
Xu
Zhizhen
Z
Huang
Gang
G
Gao
Xiang
X
Li
Song
S
He
Fengtian
F
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004731:Endotoxins / Q000633:toxicity; D024243:HMGB1 Protein / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D024243:HMGB1 Protein; D015850:Interleukin-6; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha