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Title: Nanosecond Dynamics Regulate the MIF-Induced Activity of CD74

Journal Article · · Angewandte Chemie (International Edition)
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [8];  [9]; ORCiD logo [10]
  1. Yale Univ., New Haven, CT (United States). School of Medicine, Dept. of Pharmacology
  2. Yale Univ., New Haven, CT (United States). Dept. of Chemistry; Univ. of New South Wales, Sydney (Australia). School of Chemistry
  3. Drexel Univ. College of Medicine, Philadelphia, PA (United States). Dept. of Pediatrics, Sectoin of Neonatal-Perinatal Medicine
  4. Yale School of Medicine, New Haven, CT (United States). Dept. of Pediatrics
  5. Yale School of Medicine, New Haven, CT (United States). Dept. of Internal Medicine
  6. Drexel Univ. College of Medicine, Philadelphia, PA (United States). Dept. of Pediatrics, Sectoin of Neonatal-Perinatal Medicine; Yale School of Medicine, New Haven, CT (United States). Dept. of Pediatrics
  7. Yale School of Medicine, New Haven, CT (United States). Dept. of Internal Medicine; Yale School of Medicine, New Haven, CT (United States). Yale Cancer Center
  8. Yale Univ., New Haven, CT (United States). Dept. of Chemistry
  9. Yale Univ., New Haven, CT (United States). Dept. of Chemistry; Yale School of Medicine, New Haven, CT (United States). Dept. of Molecular Biophysics and Biochemistry
  10. Yale Univ., New Haven, CT (United States). School of Medicine, Dept. of Pharmacology; Yale School of Medicine, New Haven, CT (United States). Yale Cancer Center

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. Here, the reported findings provide fundamental insights on a dynamic mechanism that controls the MIF-induced activation of CD74.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Organization:
USDOE
Grant/Contract Number:
160100807
OSTI ID:
1543472
Journal Information:
Angewandte Chemie (International Edition), Vol. 57, Issue 24; ISSN 1433-7851
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 24 works
Citation information provided by
Web of Science

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Cited By (6)

The immunobiology of MIF: function, genetics and prospects for precision medicine journal June 2019
MIF family proteins in genitourinary cancer: tumorigenic roles and therapeutic potential journal March 2019
A selective small-molecule inhibitor of macrophage migration inhibitory factor-2 (MIF-2), a MIF cytokine superfamily member, inhibits MIF-2 biological activity journal October 2019
Cross-Kingdom Analysis of Diversity, Evolutionary History, and Site Selection within the Eukaryotic Macrophage Migration Inhibitory Factor Superfamily journal September 2019
Cross-Kingdom Analysis of Diversity, Evolutionary History, and Site Selection within the Eukaryotic Macrophage Migration Inhibitory Factor Superfamily text January 2019
Cross-Kingdom Analysis of Diversity, Evolutionary History, and Site Selection within the Eukaryotic Macrophage Migration Inhibitory Factor Superfamily journal September 2019

Figures / Tables (4)