title: The Structure of a Sugar Transporter of the Glucose EIIC Superfamily Provides Insight into the Elevator Mechanism of Membrane Transport.
abstract: 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.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: McCoy
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Zhenning
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Vitali
authors.initials: V
authors.lastname: Stanevich
authors.affiliation: Department of Molecular Biosciences, Center for Computational Biology, The University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Jumin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Elena J
authors.initials: EJ
authors.lastname: Levin
authors.affiliation: Department of Chemistry, College of Staten Island, Staten Island, NY 10314, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Poget
authors.affiliation: Division of Molecular Therapeutics, Department of Psychiatry, Center for Molecular Recognition, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Quick
authors.affiliation: Department of Molecular Biosciences, Center for Computational Biology, The University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Wonpil
authors.initials: W
authors.lastname: Im
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. Electronic address: mzhou@bcm.edu.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002462:Cell Membrane / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005947:Glucose / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D000072417:Protein Domains; D021381:Protein Transport; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D005947:Glucose