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Structural and functional analysis of the solute-binding protein UspC from Mycobacterium tuberculosis that is specific for amino sugars

DOI: 10.1098/rsob.160105 DOI Help

Authors: Elizabeth Fullam (of Warwick; University of Birmingham) , Ivan Prokes (University of Warwick) , Klaus Futterer (University of Birmingham) , Gurdyal S. Besra (University of Birmingham)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Open Biology , VOL 6

State: Published (Approved)
Published: June 2016
Diamond Proposal Number(s): 6388

Open Access Open Access

Abstract: Mycobacterium tuberculosis (Mtb), the aetiological agent of tuberculosis, has evolved to scavenge nutrients from the confined environment of host macrophages with mycobacterial ATP-binding cassette (ABC) transporters playing a key role in nutrient acquisition. Mtb-UspC (Rv2318) is the solute-binding protein of the essential transporter UspABC, one of four Mtb ABC transporters implicated by homology in sugar acquisition. Herein, we report the structural and functional characterization of Mtb-UspC. The 1.5 Å resolution structure of UspC reveals a two subdomain architecture that forms a highly acidic carbohydrate-substrate binding cleft. This has allowed a distinct preference of Mtb-UspC for amino sugars as determined by thermal shift analysis and solution saturation transfer difference-NMR. Taken together our data support the functional assignment of UspABC as an amino-sugar transporter. Given the limited availability of carbohydrates within the phagosomal environmental niche during Mtb intracellular infection, our studies suggest that UspABC enables Mtb to optimize the use of scarce nutrients during intracellular infection, linking essentiality of this protein to a potential role in recycling components of cell-wall peptidoglycan.

Journal Keywords: amino sugars; X-ray crystallography; Mycobacterium tuberculosis; ATP-binding cassette transporters; nutrient acquisition; peptidoglycan

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Documents:
160105.full.pdf