3GAD

Structure of apomif

Summary for 3GAD

• Entry DOI: 10.2210/pdb3gad/pdb
• Related: 3GAC
• Descriptor: Macrophage migration inhibitory factor-like protein, SULFATE ION, ACETIC ACID, ... (4 entities in total)
• Functional Keywords: macrophage migration inhibitory factor, cytokine
• Biological source: Plasmodium yoelii yoelii
• Total number of polymer chains: 6
• Total formula weight: 78568.17

Authors

Zhou, Y.-F.,Su, X.-D.,Shao, D.,Wang, H. (deposition date: 2009-02-17, release date: 2009-12-29, Last modification date: 2023-11-01)

Primary citation

Shao, D.,Zhong, X.,Zhou, Y.-F.,Han, Z.,Lin, Y.,Wang, Z.,Bu, L.,Zhang, L.,Su, X.-D.,Wang, H.
Structural and functional comparison of MIF ortholog from Plasmodium yoelii with MIF from its rodent host
Mol.Immunol., 47:726-737, 2010

PubMed Abstract: Host-derived macrophage migration inhibitory factor (MIF) has been implicated in the pathogenesis of malaria infection, especially in malarial anemia. Although two Plasmodium parasite-derived MIF orthologs, Plasmodium falciparum MIF and P. berghei MIF were identified recently, the crystal structure and the precise roles of Plasmodium-derived MIFs, particularly in combination with the host MIF, remain unknown. In this study, we identified another MIF ortholog from a rodent-specific P. yoelii (PyMIF). This molecule shares a conserved three-dimensional structure with murine MIF (MmMIF), but with a different substrate binding pattern and much lower tautomerase activity. It could activate host cells via several signaling pathways in vitro, and inhibiting macrophage apoptosis, also similarly to MmMIF. However, we found that PyMIF and MmMIF acted synergistically to activate the MAPK-ERK1/2 signaling pathway at very low concentration but acted antagonistically at higher concentration. Furthermore, we detected PyMIF in the sera of infected mice and found that injection of recombinant PyMIF (rPyMIF) during infection could up-regulate several pro-inflammatory cytokines in vivo and slightly delay the death of infected mice. These data suggest that PyMIF modulates host immune responses together with host MIF and has potential to prolong parasitemia or the chronicity of malaria infection.

PubMed: 20004020
DOI: 10.1016/j.molimm.2009.10.037

Experimental method

X-RAY DIFFRACTION (1.8 Å)