Abstract

BackgroundThe human (Homo sapiens) chemokine-like protein macrophage migration inhibitory factor (HsMIF) is a pivotal mediator of inflammatory, infectious and immune diseases including septic shock, colitis, malaria, rheumatoid arthritis, and atherosclerosis, as well as tumorigenesis. HsMIF has been found to exhibit several sequential and three-dimensional sequence motifs that in addition to its receptor binding sites include catalytic sites for oxidoreductase and tautomerase activity, which provide this 12.5 kDa protein with a remarkable functional complexity. A human MIF paralog, D-dopachrome tautomerase (HsDDT), has been identified, but its physiological relevance is incompletely understood. MIF/DDT-like proteins have been described in animals, protists and bacteria. Although based on sequence data banks the presence of MIF/DDT-like proteins has also been recognized in the model plant species Arabidopsis thaliana, details on these plant proteins have not been reported.ResultsTo broaden the understanding of the biological role of these proteins across kingdoms we performed a comprehensive in silico analysis of plant MIF/DDT-like (MDL) genes/proteins. We found that the A. thaliana genome harbors three MDL genes, of which two are chiefly constitutively expressed in aerial plant organs, while the third gene shows stress-inducible transcript accumulation. The product of the latter gene likely localizes to peroxisomes. Structure prediction suggests that all three Arabidopsis proteins resemble the secondary and tertiary structure of human MIF. MIF-like proteins are found in all species across the plant kingdom, with an increasing family complexity towards evolutionarily advanced plant taxa. Plant MDL proteins are predicted to lack oxidoreductase activity, but possibly share tautomerase activity with human MIF/DDT.ConclusionsPeroxisome localization seems to be a specific feature of a subset of MIF/DDT orthologs found in dicotyledonous plant species, which together with its stress-inducible gene expression might point to convergent evolution in higher plants and vertebrates towards neofunctionalization of MIF/MDL proteins in stress response pathways including innate immunity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0337-x) contains supplementary material, which is available to authorized users.

Highlights

  • The human (Homo sapiens) chemokine-like protein macrophage migration inhibitory factor (HsMIF) is a pivotal mediator of inflammatory, infectious and immune diseases including septic shock, colitis, malaria, rheumatoid arthritis, and atherosclerosis, as well as tumorigenesis

  • Macrophage migration inhibitory factor (MIF) is an evolutionarily ancient protein that is best known for its functions as an immune and inflammatory factor and that was more recently recognized to have chemokine-like properties to regulate a plethora of processes in the biology and pathophysiology of humans [10,11]

  • HsMIF is a pivotal mediator of inflammatory, infectious and immune diseases including septic shock, colitis, malaria, rheumatoid arthritis, and atherosclerosis, as well as in several tumors [14,17]

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Summary

Introduction

The human (Homo sapiens) chemokine-like protein macrophage migration inhibitory factor (HsMIF) is a pivotal mediator of inflammatory, infectious and immune diseases including septic shock, colitis, malaria, rheumatoid arthritis, and atherosclerosis, as well as tumorigenesis. Macrophage migration inhibitory factor (MIF) is an evolutionarily ancient protein that is best known for its functions as an immune and inflammatory factor and that was more recently recognized to have chemokine-like properties to regulate a plethora of processes in the biology and pathophysiology of humans [10,11]. HsMIF is a pivotal mediator of inflammatory, infectious and immune diseases including septic shock, colitis, malaria, rheumatoid arthritis, and atherosclerosis, as well as in several tumors [14,17]. MIF functions are mediated through three receptor proteins: on the one hand, MIF signals through the type II receptor protein CD74/invariant chain, but on the other hand it serves as a non-cognate ligand for the classical CXC chemokine receptors CXCR2 and CXCR4 [19,20]

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