The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study

© 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 characterize...

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Main Authors: Anggayasti, W., Mancera, Ricardo, Bottomley, S., Helmerhorst, Erik
Format: Journal Article
Published: Elsevier BV 2016
Online Access:http://hdl.handle.net/20.500.11937/26456
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author Anggayasti, W.
Mancera, Ricardo
Bottomley, S.
Helmerhorst, Erik
author_facet Anggayasti, W.
Mancera, Ricardo
Bottomley, S.
Helmerhorst, Erik
author_sort Anggayasti, W.
building Curtin Institutional Repository
collection Online Access
description © 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.
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spelling curtin-20.500.11937-264562017-09-13T15:26:49Z The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study Anggayasti, W. Mancera, Ricardo Bottomley, S. Helmerhorst, Erik © 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. 2016 Journal Article http://hdl.handle.net/20.500.11937/26456 10.1016/j.bbapap.2016.07.008 Elsevier BV restricted
spellingShingle Anggayasti, W.
Mancera, Ricardo
Bottomley, S.
Helmerhorst, Erik
The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study
title The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study
title_full The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study
title_fullStr The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study
title_full_unstemmed The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study
title_short The effect of physicochemical factors on the self-association of HMGB1: A surface plasmon resonance study
title_sort effect of physicochemical factors on the self-association of hmgb1: a surface plasmon resonance study
url http://hdl.handle.net/20.500.11937/26456