Oxidation State Dependent Conformational Changes of HMGB1 Regulate the Formation of the CXCL12/HMGB1 Heterocomplex.

Details

Serval ID
serval:BIB_59DF5B7C4E43
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Oxidation State Dependent Conformational Changes of HMGB1 Regulate the Formation of the CXCL12/HMGB1 Heterocomplex.
Journal
Computational and structural biotechnology journal
Author(s)
Fassi EMA, Sgrignani J., D'Agostino G., Cecchinato V., Garofalo M., Grazioso G., Uguccioni M., Cavalli A.
ISSN
2001-0370 (Print)
ISSN-L
2001-0370
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
17
Pages
886-894
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
High-mobility Group Box 1 (HMGB1) is an abundant protein present in all mammalian cells and involved in several processes. During inflammation or tissue damage, HMGB1 is released in the extracellular space and, depending on its redox state, can form a heterocomplex with CXCL12. The heterocomplex acts exclusively via the chemokine receptor CXCR4 enhancing leukocyte recruitment. Here, we used multi-microsecond molecular dynamics (MD) simulations to elucidate the effect of the disulfide bond on the structure and dynamics of HMGB1. The results of the MD simulations show that the presence or lack of the disulfide bond between Cys23 and Cys45 modulates the conformational space explored by HMGB1, making the reduced protein more suitable to form a complex with CXCL12.
Keywords
CXCL12, CXCL12, C-X-C motif chemokine 12, CXCR4, C-X-C chemokine receptor type 4, Conformational ensemble, HMGB1, HMGB1, High-mobility Group Box 1, MD, Molecular dynamics, Molecular dynamics, Protein-protein docking, RMSD, Root mean square deviation, RoG, Radius of gyration, SASA, Solvent accessible surface area, TLR2 or TLR4, Toll-like Receptor 2 or 4, ds-HMGB1, Disulfide High-mobility Group Box 1, fr-HMGB1, Full reduced High-mobility Group Box 1
Pubmed
Open Access
Yes
Create date
19/08/2019 9:48
Last modification date
21/08/2019 6:17
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