文章基本信息

标题：Oxidation State Dependent Conformational Changes of HMGB1 Regulate the Formation of the CXCL12/HMGB1 Heterocomplex
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作者：Enrico M.A. Fassi ; Jacopo Sgrignani ; Gianluca D'Agostino 等
期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2019
卷号：17
页码：886-894
DOI：10.1016/j.csbj.2019.06.020
出版社：Computational and Structural Biotechnology Journal
摘要：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.
关键词：HMGB1 ; CXCL12 ; Molecular dynamics ; Protein-protein docking ; Conformational ensemble ; HMGB1 High-mobility Group Box 1 ; fr-HMGB1 Full reduced High-mobility Group Box 1 ; ds-HMGB1 Disulfide High-mobility Group Box 1 ; CXCL12 C-X-C motif chemokine 12 ; CXCR4 C-X-C chemokine receptor type 4 ; TLR2 or TLR4 Toll-like Receptor 2 or 4 ; MD Molecular dynamics ; RMSD Root mean square deviation ; SASA Solvent accessible surface area ; RoG Radius of gyration