Nanosecond Dynamics Regulate the MIF‐Induced Activity of CD74. (9th May 2018)

• Record Type: Journal Article
• Authors: Pantouris, Georgios; Ho, Junming; Shah, Dilip; Syed, Mansoor Ali; Leng, Lin; Bhandari, Vineet; Bucala, Richard; Batista, Victor S.; Loria, J. Patrick; Lolis, Elias J.
• Is Part Of: Angewandte Chemie. Volume 130:Number 24(2018)
• Page Start: 7234
• Page End: 7237
• Publication Date: 2018-05-09
• Subjects: Allosterische Zentren -- Langreichweitige Kommunikation -- MIF -- Proteindynamik; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201803191
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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.