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

Pantouris G, Syed MA, Fan C, Rajasekaran D, Cho TY, Rosenberg EM, Bucala R, Bhandari V, Lolis EJ
Chem Biol 22 1197-205 (2015)
Related entries: 4p01, 4p0h, 4pkz, 4plu, 4trf, 4tru, 4xx7, 5bs9, 5bsc, 5bsi

Cited: 47 times
EuropePMC logo PMID: 26364929

Abstract

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.

Articles - 4xx8 mentioned but not cited (2)

  1. An Analysis of MIF Structural Features that Control Functional Activation of CD74. Pantouris G, Syed MA, Fan C, Rajasekaran D, Cho TY, Rosenberg EM, Bucala R, Bhandari V, Lolis EJ. Chem Biol 22 1197-1205 (2015)
  2. The N-terminus of MIF regulates the dynamic profile of residues involved in CD74 activation. Parkins A, Skeens E, McCallum CM, Lisi GP, Pantouris G. Biophys J 120 3893-3900 (2021)


Reviews citing this publication (11)

  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. Granulocytes: New Members of the Antigen-Presenting Cell Family. Lin A, Loré K. Front Immunol 8 1781 (2017)
  4. 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)
  5. Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus. Bilsborrow JB, Doherty E, Tilstam PV, Bucala R. Expert Opin Ther Targets 23 733-744 (2019)
  6. MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics. Tilstam PV, Qi D, Leng L, Young L, Bucala R. Expert Opin Ther Targets 21 671-683 (2017)
  7. Small-molecule inhibitors of macrophage migration inhibitory factor (MIF) as an emerging class of therapeutics for immune disorders. Kok T, Wasiel AA, Cool RH, Melgert BN, Poelarends GJ, Dekker FJ. Drug Discov Today 23 1910-1918 (2018)
  8. Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury. Song S, Xiao Z, Dekker FJ, Poelarends GJ, Melgert BN. Cell Mol Life Sci 79 105 (2022)
  9. Molecular Level Insights Into the Structural and Dynamic Factors Driving Cytokine Function. Cui JY, Lisi GP. Front Mol Biosci 8 773252 (2021)
  10. Harnessing neutrophil plasticity for HCC immunotherapy. Ramon-Gil E, Geh D, Leslie J. Essays Biochem 67 941-955 (2023)
  11. MIF contribution to progressive brain diseases. Matejuk A, Benedek G, Bucala R, Matejuk S, Offner H, Vandenbark AA. J Neuroinflammation 21 8 (2024)

Articles citing this publication (34)



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