Structures of Leishmania major orthologues of macrophage migration inhibitory factor

Richardson, J. M., Morrison, L. S., Bland, N. D., Bruce, S., Coombs, G. H., Mottram, J. C. and Walkinshaw, M. D. (2009) Structures of Leishmania major orthologues of macrophage migration inhibitory factor. Biochemical and Biophysical Research Communications, 380(3), pp. 442-448. (doi: 10.1016/j.bbrc.2009.01.030)

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Publisher's URL: http://dx.doi.org/10.1016/j.bbrc.2009.01.030

Abstract

Leishmania major, an intracellular parasitic protozoon that infects, differentiates and replicates within macrophages, expresses two closely related MIF-like proteins. To ascertain the roles and potential differences of these two Leishmania proteins, recombinant L. major MIF1 and MIF2 have been produced and the structures resolved by X-ray crystallography. Each has a trimeric ring architecture similar to mammalian MIF, but with some structurally distinct features. LmjMIF1, but not LmjMIF2, has tautomerase activity. 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, thereby promoting parasite survival, but suggest the LmjMIFs have potentially different biological roles. Analysis of the Leishmania braziliensis genome showed that this species lacks both MIF genes. Thus MIF is not a virulence factor in all species of Leishmania

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Walkinshaw, Mr Malcolm and Morrison, Dr Lesley and Coombs, Professor Graham and Bland, Mr Nicholas and Mottram, Professor Jeremy
Authors: Richardson, J. M., Morrison, L. S., Bland, N. D., Bruce, S., Coombs, G. H., Mottram, J. C., and Walkinshaw, M. D.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Biochemical and Biophysical Research Communications
Publisher:Elsevier Inc.
ISSN:0006-291X
ISSN (Online):1090-2104
Published Online:31 January 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
454141Analysing the roles of petidases in Leishmania infectivity and pathogenicityJeremy MottramMedical Research Council (MRC)G0700127Infection Immunity and Inflammation Life Sciences