on July 22, 2019
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 on the chemokine receptor CXCR4 enhancing leukocyte recruitment. In this article, multi-microsecond molecular dynamics (MD) simulations was used 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. These results have been reported into Computational and Structural Biology Journal.
|Graphical summary of the results, the blue arrow indicates that the corresponding heterocomplex can bind a CXCR4 dimer|
Oxidation State Dependent Conformational Changes of HMGB1 Regulate the Formation of the CXCL12/HMGB1 Heterocomplex
E. Fassi, J. Sgrignani, G. D’Agostino, V. Cecchinato, M. Garofalo, G. Grazioso, M. Uguccioni, A. Cavalli
in Computational and Structural Biology Journal (2019) vol. 17 pp886-894.