Homologues of human macrophage migration inhibitory factor from a parasitic nematode

Gene cloning, protein activity, and crystal structure

Xingxing Zang, Paul Taylor, Ji Ming Wang, David J. Meyer, Alan Leroy Scott, Malcolm D. Walkinshaw, Rick M. Maizels

Research output: Contribution to journalArticle

Abstract

Cytokines are the molecular messengers of the vertebrate immune system, coordinating the local and systemic immune responses to infective organisms. We report here functional and structural data on cytokinelike proteins from a eukaryotic pathogen. Two homologues of the human cytokine macrophage migration inhibitory factor (MIF) have been isolated from the parasitic nematode Brugia malayi. Both molecules (Bm-MIF-1 and Bm-MIF-2) show parallel functions to human MIF. They are chemotactic for human monocytes and activate them to produce IL-8, TNF-α, and endogenous MIF. The human and nematode MIF homologues share a tautomerase enzyme activity, which is in each case abolished by the mutation of the N-terminal proline residue. The crystal structure of Bm-MIF-2 at 1.8-Å resolution has been determined, revealing a trimeric assembly with an inner pore created by β-stranded sheets from each subunit. Both biological activity and crystal structure reveal remarkable conservation between a human cytokine and its parasite counterpart despite the considerable phylogenetic divide among these organisms. The strength of the similarity implies that MIF-mediated pathways play an important role in nematode immune evasion strategies.

Original languageEnglish (US)
Pages (from-to)44261-44267
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number46
DOIs
StatePublished - Nov 15 2002

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Macrophage Migration-Inhibitory Factors
Cloning
Organism Cloning
Genes
Crystal structure
Cytokines
Proteins
Human Migration
Immune system
Enzyme activity
Brugia malayi
Pathogens
Bioactivity
Interleukin-8
Immune Evasion
Proline
Conservation
Vertebrates
Monocytes
Immune System

ASJC Scopus subject areas

  • Biochemistry

Cite this

Homologues of human macrophage migration inhibitory factor from a parasitic nematode : Gene cloning, protein activity, and crystal structure. / Zang, Xingxing; Taylor, Paul; Wang, Ji Ming; Meyer, David J.; Scott, Alan Leroy; Walkinshaw, Malcolm D.; Maizels, Rick M.

In: Journal of Biological Chemistry, Vol. 277, No. 46, 15.11.2002, p. 44261-44267.

Research output: Contribution to journalArticle

Zang, Xingxing ; Taylor, Paul ; Wang, Ji Ming ; Meyer, David J. ; Scott, Alan Leroy ; Walkinshaw, Malcolm D. ; Maizels, Rick M. / Homologues of human macrophage migration inhibitory factor from a parasitic nematode : Gene cloning, protein activity, and crystal structure. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 46. pp. 44261-44267.
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