Nanosecond Dynamics Regulate the MIF-Induced Activity of CD74.

Nanosecond Dynamics Regulate the MIF-Induced Activity of CD74.
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DOI:
10.1002/anie.201803191
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发表时间:
2018-06-11
期刊:
Angewandte Chemie (International ed. in English)
影响因子:
--
通讯作者:
Lolis EJ
Lolis EJ
中科院分区:
其他
文献类型:
--
作者:
Pantouris G;Ho J;Shah D;Syed MA;Leng L;Bhandari V;Bucala R;Batista VS;Loria JP;Lolis EJ

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巨噬细胞移动抑制因子(MIF)激活CD74,这导致严重的疾病,包括炎症、自身免疫性疾病和病理条件下的癌症。分子动力学(MD)模拟高达1微秒揭示了位于MIF溶剂通道一端开口处的残基(以前认为是同源三聚化的结果)与负责CD74活化的远端区域中的残基之间的动态相关性。实验验证了变构调节位点,并鉴定了通过MIF β链到达该位点的途径。报道的发现提供了关于控制MIF诱导的CD74活化的动态机制的基本见解。Pantouris及其同事描述了一个变构位点和一种MIF控制CD74活化的动力学机制
Macrophage migration inhibitory factor (MIF) activates CD74, which leads to severe disorders including inflammation, autoimmune diseases and cancer under pathological conditions. Molecular dynamics (MD) simulations up to one microsecond revealed dynamical correlation between a residue located at the opening of one end of the MIF solvent channel, previously thought to be a consequence of homotrimerization, and residues in a distal region responsible for CD74 activation. Experiments verified the allosteric regulatory site and identified a pathway to this site via the MIF β-strands. The reported findings provide fundamental insights on a dynamic mechanism that controls the MIF-induced activation of CD74. Pantouris and co-workers describe an allosteric site and a dynamic mechanism by which MIF controls activation of CD74
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