9YYA

Macrophage Migration Inhibitory Factor 1 from Necator Americanus

Summary for 9YYA

• Entry DOI: 10.2210/pdb9yya/pdb
• Descriptor: Macrophage migration inhibitory factor (2 entities in total)
• Functional Keywords: cytokine, orthologue, helminth, parasite
• Biological source: Necator americanus (New World hookworm)
• Total number of polymer chains: 12
• Total formula weight: 155495.75

Authors

Orkwis, J.A.,Lolis, E.J.,Manjula, R. (deposition date: 2025-10-28, release date: 2025-11-12, Last modification date: 2026-08-05)

Primary citation

Orkwis, J.A.,Manjula, R.,Lolis, E.J.
Helminth proteins recapitulate key structural motifs of MIF to facilitate immunomodulation of host receptors.
Iscience, 29:116513-116513, 2026

PubMed Abstract: Parasite-derived homologs of the cytokine macrophage migration inhibitory factor (MIF) function as virulent factors during parasitic infection. Recent evidence suggests MIF-like products from multicellular species can be targeted to ameliorate parasite burden. Here, we identify a broad contingent of hypothetical MIF-like proteins from genomic repositories and perform structure analysis to validate conserved homology. Further, we employ a diverse subset of MIF-specific assays to establish cross-species functionality of MIF proteins, including native enzymatic activity, binding to cognate receptor CD74, direct interactions with human MIF, and signaling through chemokine receptors CXCR2 and CXCR4. We demonstrate that MIF-like proteins retain a preserved architecture but are capable of diverse physiological outcomes due to small changes in key components of the conserved MIF structure. This work simultaneously provides a mechanistic understanding of virulence upon infection, while broadly examining the potential to neutralize MIF-like proteins for protection against various pathological species.

PubMed: 42491877
DOI: 10.1016/j.isci.2026.116513

Experimental method

X-RAY DIFFRACTION (2.098 Å)