高迁移率族蛋白B1（HMGB1）氧化态依赖性构象变化调控CXC趋化因子配体12（CXCL12）/HMGB1异源复合物的形成。

Fassi Enrico M A, Sgrignani Jacopo, D'Agostino Gianluca, Cecchinato Valentina, Garofalo Maura, Grazioso Giovanni, Uguccioni Mariagrazia, Cavalli Andrea

Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland.

University of Lausanne (UNIL), CH-1015, Lausanne, Switzerland.

Comput Struct Biotechnol J. 2019 Jun 21;17:886-894. doi: 10.1016/j.csbj.2019.06.020. eCollection 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 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.

高迁移率族蛋白B1（HMGB1）是一种在所有哺乳动物细胞中都大量存在且参与多种过程的蛋白质。在炎症或组织损伤期间，HMGB1释放到细胞外空间，并且根据其氧化还原状态，可与CXCL12形成异源复合物。该异源复合物仅通过趋化因子受体CXCR4发挥作用，增强白细胞募集。在此，我们使用多微秒分子动力学（MD）模拟来阐明二硫键对HMGB1结构和动力学的影响。MD模拟结果表明，半胱氨酸23和半胱氨酸45之间二硫键的存在或缺失调节了HMGB1探索的构象空间，使得还原态蛋白质更适合与CXCL12形成复合物。