Structural basis of trehalose recycling by the ABC transporter LpqY-SugABC

Abstract

In bacteria, adenosine 5′-triphosphate (ATP)–binding cassette (ABC) importers are essential for the uptake of nutrients including the nonreducing disaccharide trehalose, a metabolite that is crucial for the survival and virulence of several human pathogens including Mycobacterium tuberculosis. SugABC is an ABC transporter that translocates trehalose from the periplasmic lipoprotein LpqY into the cytoplasm of mycobacteria. Here, we report four high-resolution cryo–electron microscopy structures of the mycobacterial LpqY-SugABC complex to reveal how it binds and passes trehalose through the membrane to the cytoplasm. A unique feature observed in this system is the initial mode of capture of the trehalose at the LpqY interface. Uptake is achieved by a pivotal rotation of LpqY relative to SugABC, moving from an open and accessible conformation to a clamped conformation upon trehalose binding. These findings enrich our understanding as to how ABC transporters facilitate substrate transport across the membrane in Gram-positive bacteria.

Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that lipidated MetQ is required for interaction

“…al. were also not able to observe the lipid moiety of lipo-SBP in complex with an ABC transporter, despite these cryo-EM structures resolving at higher resolutions (3.30, 3.44, 3.78 Å) Liu et al, 2020 . A comparison between NmMetNI and EcMetNI in the outward-facing conformation in complex with their respective MetQ proteins reveals they have similar conformations, with RMSD of 2.2 Å over 1048 Cα atoms ( Figure 4—figure supplement 2C ).…”

“…The ABC transporter-dependent role of SBPs has been well characterized for multiple ABC transporter systems ( Hollenstein et al, 2007 ; Oldham et al, 2013 ; Sabrialabed et al, 2020 ; Liu et al, 2020 ; Nguyen et al, 2018 ; de Boer et al, 2019 ). These studies reveal conserved SBP-dependent characteristics, including that the SBP is largely responsible for substrate delivery to the ABC transporter, with concomitant stimulation of the transport coupled ATPase activity.…”

Inhibition of S. aureus Infection of Human Umbilical Vein Endothelial Cells (HUVECs) by Trehalose‐ and Glucose‐Functionalized Gold Nanoparticles

“…For example, the trehalose‐specific LpqY/SugABC transporter has a substrate binding protein (SBP), LpqY, on the bacterial surface. In Gram‐positive bacteria Mycobacterium smegmatis ( M. smegmatis ), the arrangement of LpqY (SBP) is significantly different relative to the rest of the transporter and to the SBPs found on Gram‐negative E. coil [54] . Furthermore, Gram‐negative bacteria possess an outer membrane in the cell wall, a feature which is not displayed by Gram‐positive bacteria.…”

“…In Gram-positive bacteria Mycobacterium smegmatis (M. smegmatis), the arrangement of LpqY (SBP) is significantly different relative to the rest of the transporter and to the SBPs found on Gram-negative E. coil. [54] Furthermore, Gramnegative bacteria possess an outer membrane in the cell wall, a feature which is not displayed by Gram-positive bacteria. This outer membrane may also be suspected to hinder the interaction of nanoparticles with certain transporters.…”

Structural insights as to how iron-loaded siderophores are imported into Mycobacterium tuberculosis by IrtAB

“…Interestingly, although IrtAB functions as an ABC importer, it adopts the canonical fold of type IV ABC exporters (Arnold et al, 2020), which are normally responsible for the efflux of intracellular substrates such as the multidrug resistance protein, Sav1866 (Dawson and Locher, 2006). In addition, IrtAB does not require a substrate binding protein (SBP) to capture specific substrates in the periplasmic space (Arnold et al, 2020), whereas canonical ABC importers such as maltose transporter, MBP-MalFGK 2 (Oldham et al, 2007), and trehalose transporter, LpqY-SugABC (Liu et al, 2020), require this assistance. Therefore, IrtAB can be classified as belonging to a new subfamily of ABC importers with a distinct transport mechanism.…”