Structures of Leishmania major orthologues of macrophage migration inhibitory factor.
Structures of Leishmania major orthologues of macrophage migration inhibitory factor.
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DOI：
10.1016/j.bbrc.2009.01.030
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发表时间：
2009-03-13
影响因子：
3.1
通讯作者：
Walkinshaw, Malcolm D.
中科院分区：
文献类型：
--
作者：
Richardson, Julia M.;Morrison, Lesley S.;Bland, Nicholas D.;Bruce, Sandra;Coombs, Graham H.;Mottram, Jeremy C.;Walkinshaw, Malcolm D.
硕大利什曼原虫是一种在巨噬细胞内感染、分化和复制的细胞内寄生原虫，编码两种密切相关的MIF样蛋白，其与哺乳动物MIF的氨基酸同源性仅约20%。重组L.主要的MIF 1和MIF 2已经表达，并且通过X射线晶体学解析的结构显示出类似于哺乳动物MIF的三聚体环结构，但是具有一些结构上不同的特征。LmjMIF 1，而不是LmjMIF 2，具有互变异构酶活性，表明LmjMIFs已经进化出潜在的不同生物学作用。这通过蛋白质的差异生命周期表达进一步证明。LmjMIF 2存在于所有生命周期阶段，而LmjMIF 1仅存在于无鞭毛体中，无鞭毛体是哺乳动物疾病的细胞内阶段。这些发现与寄生虫MIFs调节或规避宿主巨噬细胞反应，从而促进寄生虫存活是一致的。巴西利什曼原虫基因组显示该物种缺乏完整的MIF基因-突出表明MIF不是所有利什曼原虫物种中的毒力因子。
Leishmania major, an intracellular parasitic protozoon that infects, differentiates and replicates within macrophages, encodes two closely related MIF-like proteins, which have only ~20% amino acid identity with mammalian MIF. Recombinant L. major MIF1 and MIF2 have been expressed and the structures, resolved by X-ray crystallography, show a trimeric ring architecture similar to mammalian MIF but with some structurally distinct features. LmjMIF1, but not LmjMIF2, has tautomerase activity, indicating that the LmjMIFs have evolved potentially different biological roles. This is further demonstrated by the differential life cycle expression of the proteins. LmjMIF2 is found in all life cycle stages whereas LmjMIF1 is found exclusively in amastigotes, the intracellular stage responsible for mammalian disease. The findings are consistent with parasite MIFs modulating or circumventing the host macrophage response and thereby promoting parasite survival, however analysis of the L. braziliensis genome showed that this species lacks intact MIF genes - highlighting that MIF is not a virulence factor in all species of Leishmania.
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