A structural and functional investigation of a novel protein from Mycobacterium smegmatis implicated in mycobacterial macrophage survivability. (1st September 2014)

• Record Type: Journal Article
• Authors: Shahine, Adam; Littler, Dene; Brammananath, Rajini; Chan, Phooi Y.; Crellin, Paul K.; Coppel, Ross L.; Rossjohn, Jamie; Beddoe, Travis
• Is Part Of: Acta crystallographica. Volume 70:Part 9(2014:Sep.)
• Page Start: 2264
• Page End: 2276
• Publication Date: 2014-09-01
• Subjects: Mycobacterium smegmatis -- MSMEG_5817 -- selenomethionine -- sterol carrier protein -- PI3P; Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S139900471401092X
• Languages: English
• ISSNs: 0907-4449

Abstract

Abstract : The success of pathogenic mycobacterial species is owing in part to their ability to parasitize the generally inhospitable phagosomal environment of host macrophages, utilizing a variety of strategies to avoid their antimycobacterial capabilities and thereby enabling their survival. A recently identified gene target in Mycobacterium smegmatis, highly conserved within Mycobacterium spp. and denoted MSMEG_5817, has been found to be important for bacterial survival within host macrophages. To gain insight into its function, the crystal structure of MSMEG_5817 has been solved to 2.40 Å resolution. The structure reveals a high level of structural homology to the sterol carrier protein (SCP) family, suggesting a potential role of MSMEG_5817 in the binding and transportation of biologically relevant lipids required for bacterial survival. The lipid‐binding capacity of MSMEG_5817 was confirmed by ELISA, revealing binding to a number of phospholipids with varying binding specificities compared with Homo sapiens SCP. A potential lipid‐binding site was probed by alanine‐scanning mutagenesis, revealing structurally relevant residues and a binding mechanism potentially differing from that of the SCPs.