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

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 act...

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Detalles Bibliográficos
Autores principales: Fassi, Enrico M.A., Sgrignani, Jacopo, D'Agostino, Gianluca, Cecchinato, Valentina, Garofalo, Maura, Grazioso, Giovanni, Uguccioni, Mariagrazia, Cavalli, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2019
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617219/
https://www.ncbi.nlm.nih.gov/pubmed/31333815
http://dx.doi.org/10.1016/j.csbj.2019.06.020
Descripción
Sumario: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.

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