3t5s

Publication Abstract from PubMed

Macrophage migration inhibitory factor (MIF) is a eukaryotic cytokine that affects a broad spectrum of immune responses and its activation/inactivation is associated with numerous diseases. During protozoan infections MIF is not only expressed by the host, but, has also been observed to be expressed by some parasites and released into the host. To better understand the biological role of parasitic MIF proteins, the crystal structure of the MIF protein from Giardia lamblia (Gl-MIF), the etiological agent responsible for giardiasis, has been determined at 2.30 A resolution. The 114-residue protein adopts an alpha/beta fold consisting of a four-stranded beta-sheet with two anti-parallel alpha-helices packed against a face of the beta-sheet. An additional short beta-strand aligns anti-parallel to beta4 of the beta-sheet in the adjacent protein unit to help stabilize a trimer, the biologically relevant unit observed in all solved MIF crystal structures to date, and form a discontinuous beta-barrel. The structure of Gl-MIF is compared to the MIF structures from humans (Hs-MIF) and three Plasmodium species (falciparum, berghei, and yoelii). The structure of all five MIF proteins are generally similar with the exception of a channel that runs through the center of each trimer complex. Relative to Hs-MIF, there are differences in solvent accessibility and electrostatic potential distribution in the channel of Gl-MIF and the Plasmodium-MIFs due primarily to two "gate-keeper" residues in the parasitic MIFs. For the Plasmodium MIFs the gate-keeper residues are at positions 44 (Y-->R) and 100 (V-->D) and for Gl-MIF it is at position 100 (V-->R). If these gate-keeper residues have a biological function and contribute to the progression of parasitemia they may also form the basis for structure-based drug design targeting parasitic MIF proteins.

Crystal structure of a macrophage migration inhibitory factor from Giardia lamblia.,Buchko GW, Abendroth J, Robinson H, Zhang Y, Hewitt SN, Edwards TE, Van Voorhis WC, Myler PJ J Struct Funct Genomics. 2013 Jun;14(2):47-57. doi: 10.1007/s10969-013-9155-9., Epub 2013 May 25. PMID:23709284^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.