The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study
|dc.identifier.citation||Anggayasti, W. and Mancera, R. and Bottomley, S. and Helmerhorst, E. 2016. The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study. Biochimica et Biophysica Acta - Proteins and Proteomics. 1864 (11): pp. 1620-1629.|
© 2016 Elsevier B.V. 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 pH 4.0, 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.
|dc.title||The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study|
|dcterms.source.title||Biochimica et Biophysica Acta - Proteins and Proteomics|
|curtin.department||School of Biomedical Sciences|
|curtin.accessStatus||Fulltext not available|
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