The Structure of a Sugar Transporter of the Glucose EIIC Superfamily Provides Insight into the Elevator Mechanism of Membrane Transport

• Published in: Structure (London) Vol. 24; no. 6; pp. 956 - 964
• Main Authors: McCoy, Jason G., Ren, Zhenning, Stanevich, Vitali, Lee, Jumin, Mitra, Sharmistha, Levin, Elena J., Poget, Sebastien, Quick, Matthias, Im, Wonpil, Zhou, Ming
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 07.06.2016; Elsevier
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; BASIC BIOLOGICAL SCIENCES; Binding Sites; Carbohydrate Metabolism; Cell Membrane - metabolism; Crystallography, X-Ray; Glucose - metabolism; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - metabolism; Models, Molecular; Protein Binding; Protein Domains; Protein Transport; Substrate Specificity
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2016.04.003

The phosphoenolpyruvate:carbohydrate phosphotransferase systems are found in bacteria, where they play central roles in sugar uptake and regulation of cellular uptake processes. Little is known about how the membrane-embedded components (EIICs) selectively mediate the passage of carbohydrates across the membrane. Here we report the functional characterization and 2.55-Å resolution structure of a maltose transporter, bcMalT, belonging to the glucose superfamily of EIIC transporters. bcMalT crystallized in an outward-facing occluded conformation, in contrast to the structure of another glucose superfamily EIIC, bcChbC, which crystallized in an inward-facing occluded conformation. The structures differ in the position of a structurally conserved substrate-binding domain that is suggested to play a central role in sugar transport. In addition, molecular dynamics simulations suggest a potential pathway for substrate entry from the periplasm into the bcMalT substrate-binding site. These results provide a mechanistic framework for understanding substrate recognition and translocation for the glucose superfamily EIIC transporters. [Display omitted] •bcMalT is a selective maltose transporter belonging to the EIIC glucose superfamily•bcMalT is the first outward-facing structure of a glucose superfamily EIIC•bcMalT and previously characterized EIIC bcChbC share a similar fold•The bcMalT substrate-binding domain is displaced relative to that of bcChbC by 20 Å McCoy et al. characterize a maltose transporter from the EIIC glucose superfamily and solve its crystal structure. The structure reveals the substrate-binding site, and suggests a mechanism by which the movement of a structurally conserved domain could facilitate substrate translocation across the membrane.