title: Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG.
abstract: After biosynthesis, bacterial lipopolysaccharides (LPS) are transiently anchored to the outer leaflet of the inner membrane (IM). The ATP-binding cassette (ABC) transporter LptB2FG extracts LPS molecules from the IM and transports them to the outer membrane. Here we report the crystal structure of nucleotide-free LptB2FG from Pseudomonas aeruginosa. The structure reveals that lipopolysaccharide transport proteins LptF and LptG each contain a transmembrane domain (TMD), a periplasmic β-jellyroll-like domain and a coupling helix that interacts with LptB on the cytoplasmic side. The LptF and LptG TMDs form a large outward-facing V-shaped cavity in the IM. Mutational analyses suggest that LPS may enter the central cavity laterally, via the interface of the TMD domains of LptF and LptG, and is expelled into the β-jellyroll-like domains upon ATP binding and hydrolysis by LptB. These studies suggest a mechanism for LPS extraction by LptB2FG that is distinct from those of classical ABC transporters that transport substrates across the IM.
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Luo
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Yu
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Huigang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Institute of Bio-analytical Chemistry, School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, P.R.China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Le
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Discovery Biology, Albany Molecular Research Inc., Buffalo, New York, USA.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Chuanqi
authors.initials: C
authors.lastname: Sun
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Dianfan
authors.initials: D
authors.lastname: Li
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xinzheng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Bio-analytical Chemistry, School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, P.R.China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Huang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D008070:Lipopolysaccharides / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D008070:Lipopolysaccharides