Protein Structure and Folding
Separating cytokine twins with a small molecule
The cytokine macrophage migration inhibitory factor (MIF) has been characterized as a key immunomodulator and mediator of various diseases. Small molecule inhibitors based on the conserved enzymatic pocket of MIF have been valuable in elucidating MIF mechanisms and developing translational strategies. In contrast, our mechanistic understanding of the MIF homolog MIF-2/d-dopachrome tautomerase (d-DT) and its clinical translation has been hampered, partly because MIF-2–selective inhibitors have been elusive.Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions
An emerging number of non-chemokine mediators are found to bind to classical chemokine receptors and to elicit critical biological responses. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that exhibits chemokine-like activities through non-cognate interactions with the chemokine receptors CXCR2 and CXCR4, in addition to activating the type II receptor CD74. Activation of the MIF-CXCR2 and -CXCR4 axes promotes leukocyte recruitment, mediating the exacerbating role of MIF in atherosclerosis and contributing to the wealth of other MIF biological activities.
