A structural and functional investigation of a novel protein from Mycobacterium smegmatis implicated in mycobacterial macrophage survivability

Adam Elias Shahine, Dene Littler, Rajini Brammananth, Phooi Yeng Chan, Paul K Crellin, Ross L Coppel, Jamie Rossjohn, Travis C Beddoe

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3 Citations (Scopus)


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 A 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.
Original languageEnglish
Pages (from-to)2264 - 2276
Number of pages13
JournalActa Crystallographica Section D: Biological Crystallography
Issue number9
Publication statusPublished - 2014

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