The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study
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Updated: Mar 17, 2026
Real Time Measurements of Membrane Protein:Receptor Interactions Using Surface Plasmon Resonance SPR
Published on: November 29, 2014
Wresti L Anggayasti1, Ricardo L Mancera1, Steven Bottomley1
1School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, GPO Box U1987, Perth, WA 6845, Australia.
Abstract:
HMGB1 triggers proinflammatory reactions by interacting extracellularly with various receptors. HMGB1 also acts in the nucleus by interacting with DNA and controlling DNA transcription, a process which involves its self-association. The self-association of HMGB1 was characterized using surface plasmon resonance (SPR). A dimer/tetramer binding model was developed that provided a good fit to the SPR sensorgrams and enabled the kinetics of self-association of different HMGB1 oligomers to be evaluated under a variety of physicochemical conditions. The formation of HMGB1 tetramers, and not dimers, was strongly influenced by ionic strength. HMGB1 self-association increased as the pH was decreased from 7.4 to 4.8 but was abolished at pH4.0, suggesting the involvement of acidic amino acids of HMGB1 in its self-association. HMGB1 dimers were found to predominate in the absence of zinc, but addition of zinc promoted the formation of HMGB1 tetramers. More reducing conditions favored dimerization but diminished tetramer formation. In contrast, oxidizing conditions favored tetramer formation. Physicochemical factors modulate the extent of self-association of HMGB1. We speculate that HMGB1 dimers may preferentially bind DNA, whereas HMGB1 tetramers may promote inflammatory responses by binding to RAGE and TLRs. The self-association of HMGB1, regulated by variations of physicochemical factors, may influence its roles in DNA rearrangement and regulation of pathophysiological diseases.
Insights
High-mobility group box 1 (HMGB1) protein self-association is modulated by physicochemical factors. This self-association influences HMGB1
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- High-mobility group box 1 (HMGB1) protein plays dual roles in both nuclear functions and extracellular inflammatory responses.
- HMGB1's extracellular interactions with receptors like RAGE and TLRs trigger inflammation.
- Nuclear HMGB1 interacts with DNA, regulating transcription through self-association.
Purpose of the Study:
- To characterize the self-association of HMGB1 using biophysical techniques.
- To investigate the influence of various physicochemical factors on HMGB1 oligomerization.
- To correlate HMGB1 self-association states with its proposed functions.
Main Methods:
- Surface Plasmon Resonance (SPR) was employed to study HMGB1 self-association kinetics.
- A dimer/tetramer binding model was developed to analyze SPR data.
- HMGB1 self-association was evaluated under varying ionic strength, pH, zinc concentration, and redox conditions.
Main Results:
- Physicochemical factors significantly modulate HMGB1 self-association into dimers and tetramers.
- Ionic strength and pH strongly influence tetramer formation, while zinc addition promotes it.
- Redox conditions affect the dimer/tetramer equilibrium, with oxidizing conditions favoring tetramers.
Conclusions:
- HMGB1 self-association is a dynamic process regulated by its environment.
- HMGB1 dimers may be involved in DNA binding and transcription regulation.
- HMGB1 tetramers are speculated to mediate inflammatory responses via receptor interactions.
- Understanding HMGB1 oligomerization provides insights into its roles in DNA dynamics and disease pathogenesis.
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