Modeling of both shared and distinct interactions between MIF and its homologue D-DT with their common receptor CD74.

ABSTRACT: D-dopachrome tautomerase (D-DT) shares amino acid sequence similarity, structural architecture and biological activity with the cytokine MIF. Recent studies show that the two protein homologs also bind to the same cell surface receptor, CD74, to activate the ERK1/2 pathway that ultimately leads to pro-inflammatory and pro-survival gene expression. We recently showed that RTL1000 and DRa1-MOG-35-55, two biological drugs with potent anti-inflammatory properties that treat experimental autoimmune encephalomyelitis (EAE) in mice, bind to the cell surface receptor CD74 with high affinity and compete with MIF for binding to the same regions of CD74. Computational modeling of MIF and RTL1000 binding interactions with CD74 predicted the presence of three CD74 binding regions for each MIF homotrime

SUBMITTER: Meza-Romero R 

PROVIDER: S-EPMC5067215 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature