Amino acid residues 201-205 in C-terminal acidic tail region plays a crucial role in antibacterial activity of HMGB1.

Amino acid residues 201-205 in C-terminal acidic tail region plays a crucial role in antibacterial activity of HMGB1.
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C端酸性尾区的氨基酸残基201-205在HMGB1的抗菌活性中起着至关重要的作用

DOI:
10.1186/1423-0127-16-83
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发表时间:
2009-09-14
影响因子:
11
通讯作者:
He F
He F
中科院分区:
医学1区
文献类型:
--
作者:
Gong W;Li Y;Chao F;Huang G;He F

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抗菌活性是高迁移率族蛋白1(HMGB 1)的一种新功能。方法和结果本研究利用原核表达系统制备了重组人HMGB 1 A box和B box(rHMGB 1 A box,rHMGB 1 B box)、重组人HMGB 1(rHMGB 1)和截短C端酸性尾突变体(tHMGB 1)。合成了由30个氨基酸残基组成的C-末端酸性尾(C肽)。抑菌试验表明,rHMGB 1全长和合成C肽单独使用均能有效抑制细菌增殖,而rHMGB 1 A box和B box以及缺失C端酸性尾的tHMGB 1则无抑菌作用。这些结果表明,C端酸性尾是HMGB 1抗菌活性的关键区域。此外,我们还制备了11个不同的缺失突变体,它们在HMGB 1的C-末端酸性尾部缺失了几个氨基酸残基。对这些突变体的抑菌实验表明,HMGB 1 C端酸性尾区201-205位氨基酸残基是其抗菌活性的核心功能位点。结论这些结果明确了HMGB 1抗菌活性的关键区域和关键位点,有助于阐明HMGB 1的抗菌机制。
BackgroundAntibacterial activity is a novel function of high-mobility group box 1 (HMGB1). However, the functional site for this new effect is presently unknown.Methods and ResultsIn this study, recombinant human HMGB1 A box and B box (rHMGB1 A box, rHMGB1 B box), recombinant human HMGB1 (rHMGB1) and the truncated C-terminal acidic tail mutant (tHMGB1) were prepared by the prokaryotic expression system. The C-terminal acidic tail (C peptide) was synthesized, which was composed of 30 amino acid residues. Antibacterial assays showed that both the full length rHMGB1 and the synthetic C peptide alone could efficiently inhibit bacteria proliferation, but rHMGB1 A box and B box, and tHMGB1 lacking the C-terminal acidic tail had no antibacterial function. These results suggest that C-terminal acidic tail is the key region for the antibacterial activity of HMGB1. Furthermore, we prepared eleven different deleted mutants lacking several amino acid residues in C-terminal acidic tail of HMGB1. Antibacterial assays of these mutants demonstrate that the amino acid residues 201-205 in C-terminal acidic tail region is the core functional site for the antibacterial activity of the molecule.ConclusionIn sum, these results define the key region and the crucial site in HMGB1 for its antibacterial function, which is helpful to illustrating the antibacterial mechanisms of HMGB1.
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