A computational assessment of the predicted structures of Human Macrophage Migration Inhibitory Factor 1 orthologs in parasites and its affinity to human CD74 receptor. Issue 10 (17th May 2017)

• Record Type: Journal Article
• Authors: Machicado, Claudia; Marcos, Luis A.
• Is Part Of: Journal of molecular recognition. Volume 30:Issue 10(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-05-17
• Subjects: CD74 -- electrostatic potential -- homology modelling -- macrophage migration‐Inhibitory Factor -- molecular docking; Molecular recognition -- Periodicals; Models, Molecular -- Periodicals; Molecular Conformation -- Periodicals; Molecular Sequence Data -- Periodicals; Molecular Structure -- Periodicals; Carrier Proteins -- Periodicals; 572.8
• DOI: 10.1002/jmr.2640
• Languages: English
• ISSNs: 0952-3499

Abstract

Abstract: The human macrophage migration inhibitory factor 1 (Hu‐MIF‐1) is a protein involved in the inflammatory and immunology response to parasite infection. In the present study, the existence of Hu‐MIF‐1 from parasites have been explored by mining WormBase. A total of 35 helminths were found to have Hu‐MIF‐1 homologs, including some parasites of importance for public health. Physicochemical, structural, and biological properties of Hu‐MIF‐1 were compared with its orthologs in parasites showing that most of these are secretory proteins, with positive net charge and presence of the Cys‐Xaa‐Xaa‐Cys motif that is critical for its oxidoreductase activity. The inhibitor‐binding site present in Hu‐MIF‐1 is well conserved among parasite MIFs suggesting that Hu‐MIF inhibitors may target orthologs in pathogens. The binding of Hu‐MIF‐1 to its cognate receptor CD74 was predicted by computer‐assisted docking, and it resulted to be very similar to the predicted complexes formed by parasite MIFs and human CD74. More than 1 plausible conformation of MIFs in the extracellular loops of CD74 may be possible as demonstrated by the different predicted conformations of MIF orthologs in complex with CD74. Parasite MIFs in complex with CD74 resulted with some charged residues oriented to CD74, which was not observed in the Hu‐MIF‐1/CD74 complex. Our findings predict the binding mode of Hu‐MIF‐1 and orthologs with CD74, which can assist in the design of novel MIF inhibitors. Whether the parasite MIFs function specifically subvert host immune responses to suit the parasite is an open question that needs to be further investigated. Future research should lead to a better understanding of parasite MIF action in the parasite biology. Abstract : Human MIFs and orthologs in parasites were analyzed in their biological properties and ability to bind to human CD74. Similarities in the biological features and binding to CD74 found between human MIF and their counterparts in parasites may explain how some microorganisms subvert host immune responses to favor the pathogen growth. These similarities are useful for the discovery of novel MIF inhibitors.