4p01 Citations

An Analysis of MIF Structural Features that Control Functional Activation of CD74.

Chem. Biol. 22 1197-205 (2015)
Related entries: 4xx8, 5bsi, 4plu, 5bsc, 4xx7, 4p0h, 5bs9, 4pkz, 4tru, 4trf

Cited: 10 times
EuropePMC logo PMID: 26364929


For more than 15 years, the tautomerase active site of macrophage migration inhibitory factor (MIF) and its catalytic residue Pro1 have been being targeted for the development of therapeutics that block activation of its cell surface receptor, CD74. Neither the biological role of the MIF catalytic site nor the mechanistic details of CD74 activation are well understood. The inherently unstable structure of CD74 remains the biggest obstacle in structural studies with MIF for understanding the basis of CD74 activation. Using a novel approach, we elucidate the mechanistic details that control activation of CD74 by MIF surface residues and identify structural parameters of inhibitors that reduce CD74 biological activation. We also find that N-terminal mutants located deep in the catalytic site affect surface residues immediately outside the catalytic site, which are responsible for reduction of CD74 activation.

Reviews citing this publication (3)

  1. The biological function and significance of CD74 in immune diseases. Su H, Na N, Zhang X, Zhao Y. Inflamm. Res. 66 209-216 (2017)
  2. Targeting MIF in Cancer: Therapeutic Strategies, Current Developments, and Future Opportunities. O'Reilly C, Doroudian M, Mawhinney L, Donnelly SC. Med Res Rev 36 440-460 (2016)
  3. MIF, a controversial cytokine: a review of structural features, challenges, and opportunities for drug development. Bloom J, Sun S, Al-Abed Y. Expert Opin. Ther. Targets 20 1463-1475 (2016)

Articles citing this publication (7)

  1. Predicted structure of MIF/CD74 and RTL1000/CD74 complexes. Meza-Romero R, Benedek G, Leng L, Bucala R, Vandenbark AA. Metab Brain Dis 31 249-255 (2016)
  2. Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions: EVIDENCE FOR PARTIAL ALLOSTERIC AGONISM IN COMPARISON WITH CXCL12 CHEMOKINE. Rajasekaran D, Gröning S, Schmitz C, Zierow S, Drucker N, Bakou M, Kohl K, Mertens A, Lue H, Weber C, Xiao A, Luker G, Kapurniotu A, Lolis E, Bernhagen J. J. Biol. Chem. 291 15881-15895 (2016)
  3. Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer's Disease. Kassaar O, Pereira Morais M, Xu S, Adam EL, Chamberlain RC, Jenkins B, James T, Francis PT, Ward S, Williams RJ, van den Elsen J. Sci Rep 7 42874 (2017)
  4. A Fluorescence Polarization Assay for Binding to Macrophage Migration Inhibitory Factor and Crystal Structures for Complexes of Two Potent Inhibitors. Cisneros JA, Robertson MJ, Valhondo M, Jorgensen WL. J. Am. Chem. Soc. 138 8630-8638 (2016)
  5. Modeling of both shared and distinct interactions between MIF and its homologue D-DT with their common receptor CD74. Meza-Romero R, Benedek G, Jordan K, Leng L, Pantouris G, Lolis E, Bucala R, Vandenbark AA. Cytokine 88 62-70 (2016)
  6. Structural basis for decreased induction of class IB PI3-kinases expression by MIF inhibitors. Singh AK, Pantouris G, Borosch S, Rojanasthien S, Cho TY. J. Cell. Mol. Med. 21 142-153 (2017)
  7. A computational assessment of the predicted structures of Human Macrophage Migration Inhibitory Factor 1 orthologs in parasites and its affinity to human CD74 receptor. Machicado C, Marcos LA. J. Mol. Recognit. 30 (2017)