5iva Citations

Structural and Functional Characterization of the LPS Transporter LptDE from Gram-Negative Pathogens.

Structure 24 965-976 (2016)
Related entries: 5iv8, 5iv9, 5ixm

Cited: 82 times
EuropePMC logo PMID: 27161977

Abstract

Incorporation of lipopolysaccharide (LPS) into the outer membrane of Gram-negative bacteria is essential for viability, and is accomplished by a two-protein complex called LptDE. We solved crystal structures of the core LptDE complexes from Yersinia pestis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and a full-length structure of the K. pneumoniae LptDE complex. Our structures adopt the same plug and 26-strand β-barrel architecture found recently for the Shigella flexneri and Salmonella typhimurium LptDE structures, illustrating a conserved fold across the family. A comparison of the only two full-length structures, SfLptDE and our KpLptDE, reveals a 21° rotation of the LptD N-terminal domain that may impart flexibility on the trans-envelope LptCAD scaffold. Utilizing mutagenesis coupled to an in vivo functional assay and molecular dynamics simulations, we demonstrate the critical role of Pro231 and Pro246 in the function of the LptD lateral gate that allows partitioning of LPS into the outer membrane.

Reviews - 5iva mentioned but not cited (1)

  1. Insertion of proteins and lipopolysaccharide into the bacterial outer membrane. Botos I, Noinaj N, Buchanan SK. Philos Trans R Soc Lond B Biol Sci 372 20160224 (2017)

Articles - 5iva mentioned but not cited (7)

  1. Structural and Functional Characterization of the LPS Transporter LptDE from Gram-Negative Pathogens. Botos I, Majdalani N, Mayclin SJ, McCarthy JG, Lundquist K, Wojtowicz D, Barnard TJ, Gumbart JC, Buchanan SK. Structure 24 965-976 (2016)
  2. Deprivation of the Periplasmic Chaperone SurA Reduces Virulence and Restores Antibiotic Susceptibility of Multidrug-Resistant Pseudomonas aeruginosa. Klein K, Sonnabend MS, Frank L, Leibiger K, Franz-Wachtel M, Macek B, Trunk T, Leo JC, Autenrieth IB, Schütz M, Bohn E. Front Microbiol 10 100 (2019)
  3. Presence of substrate aids lateral gate separation in LptD. Lundquist KP, Gumbart JC. Biochim Biophys Acta Biomembr 1862 183025 (2020)
  4. Efflux Pumps Represent Possible Evolutionary Convergence onto the β-Barrel Fold. Franklin MW, Nepomnyachiy S, Feehan R, Ben-Tal N, Kolodny R, Slusky JSG. Structure 26 1266-1274.e2 (2018)
  5. Defects in Efflux (oprM), β-Lactamase (ampC), and Lipopolysaccharide Transport (lptE) Genes Mediate Antibiotic Hypersusceptibility of Pseudomonas aeruginosa Strain Z61. Shen X, Johnson NV, Kreamer NNK, Barnes SW, Walker JR, Woods AL, Six DA, Dean CR. Antimicrob Agents Chemother 63 e00784-19 (2019)
  6. A novel structurally identified epitope delivered by macrophage membrane-coated PLGA nanoparticles elicits protection against Pseudomonas aeruginosa. Gao C, Chen Y, Cheng X, Zhang Y, Zhang Y, Wang Y, Cui Z, Liao Y, Luo P, Wu W, Wang C, Zeng H, Zou Q, Gu J. J Nanobiotechnology 20 532 (2022)
  7. Antibacterial effects assessment on some livestock pathogens, thermal stability and proposing a probable reason for different levels of activity of thanatin. Javadmanesh A, Mohammadi E, Mousavi Z, Azghandi M, Tanhaiean A. Sci Rep 11 10890 (2021)


Reviews citing this publication (29)

  1. Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes. Wong LH, Gatta AT, Levine TP. Nat Rev Mol Cell Biol 20 85-101 (2019)
  2. Emerging Diversity in Lipid-Protein Interactions. Corradi V, Sejdiu BI, Mesa-Galloso H, Abdizadeh H, Noskov SY, Marrink SJ, Tieleman DP. Chem Rev 119 5775-5848 (2019)
  3. Outer Membrane Biogenesis. Konovalova A, Kahne DE, Silhavy TJ. Annu Rev Microbiol 71 539-556 (2017)
  4. Assembly and Maintenance of Lipids at the Bacterial Outer Membrane. Lundstedt E, Kahne D, Ruiz N. Chem Rev 121 5098-5123 (2021)
  5. The lipopolysaccharide transport (Lpt) machinery: A nonconventional transporter for lipopolysaccharide assembly at the outer membrane of Gram-negative bacteria. Sperandeo P, Martorana AM, Polissi A. J Biol Chem 292 17981-17990 (2017)
  6. Intermembrane transport: Glycerophospholipid homeostasis of the Gram-negative cell envelope. Powers MJ, Trent MS. Proc Natl Acad Sci U S A 116 17147-17155 (2019)
  7. The Treponema pallidum Outer Membrane. Radolf JD, Kumar S. Curr Top Microbiol Immunol 415 1-38 (2018)
  8. Targeting the Sugary Armor of Klebsiella Species. Patro LPP, Rathinavelan T. Front Cell Infect Microbiol 9 367 (2019)
  9. Border Control: Regulating LPS Biogenesis. Guest RL, Rutherford ST, Silhavy TJ. Trends Microbiol 29 334-345 (2021)
  10. Folded Synthetic Peptides and Other Molecules Targeting Outer Membrane Protein Complexes in Gram-Negative Bacteria. Robinson JA. Front Chem 7 45 (2019)
  11. Inter-organelle lipid transfer: a channel model for Vps13 and chorein-N motif proteins. Lees JA, Reinisch KM. Curr Opin Cell Biol 65 66-71 (2020)
  12. Modeling and simulation of bacterial outer membranes and interactions with membrane proteins. Patel DS, Qi Y, Im W. Curr Opin Struct Biol 43 131-140 (2017)
  13. Structural Basis for the Lipopolysaccharide Export Activity of the Bacterial Lipopolysaccharide Transport System. Hicks G, Jia Z. Int J Mol Sci 19 E2680 (2018)
  14. New treatments of multidrug-resistant Gram-negative ventilator-associated pneumonia. Poulakou G, Lagou S, Karageorgopoulos DE, Dimopoulos G. Ann Transl Med 6 423 (2018)
  15. Modulators of protein-protein interactions as antimicrobial agents. Kahan R, Worm DJ, de Castro GV, Ng S, Barnard A. RSC Chem Biol 2 387-409 (2021)
  16. Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels. Egea PF. Front Cell Dev Biol 9 784367 (2021)
  17. Proteomics, Bioinformatics and Structure-Function Antigen Mining For Gonorrhea Vaccines. Baarda BI, Martinez FG, Sikora AE. Front Immunol 9 2793 (2018)
  18. The surface lipoproteins of gram-negative bacteria: Protectors and foragers in harsh environments. Cole GB, Bateman TJ, Moraes TF. J Biol Chem 296 100147 (2021)
  19. Airway immunometabolites fuel Pseudomonas aeruginosa infection. Riquelme SA, Prince A. Respir Res 21 326 (2020)
  20. High-resolution views of lipopolysaccharide translocation driven by ABC transporters MsbA and LptB2FGC. Thélot F, Orlando BJ, Li Y, Liao M. Curr Opin Struct Biol 63 26-33 (2020)
  21. Structural features underlying recognition and translocation of extracellular polysaccharides. Zimmer J. Interface Focus 9 20180060 (2019)
  22. What have molecular simulations contributed to understanding of Gram-negative bacterial cell envelopes? Khalid S, Schroeder C, Bond PJ, Duncan AL, Duncan AL. Microbiology (Reading) 168 (2022)
  23. Perspective: Computational modeling of accurate cellular membranes with molecular resolution. Klauda JB. J Chem Phys 149 220901 (2018)
  24. Structure and mechanism of the bacterial lipid ABC transporter, MlaFEDB. Ekiert DC, Coudray N, Bhabha G. Curr Opin Struct Biol 76 102429 (2022)
  25. In silico investigation and surmounting of Lipopolysaccharide barrier in Gram-Negative Bacteria: How far has molecular dynamics Come? González-Fernández C, Bringas E, Oostenbrink C, Ortiz I. Comput Struct Biotechnol J 20 5886-5901 (2022)
  26. Bacterial AsmA-Like Proteins: Bridging the Gap in Intermembrane Phospholipid Transport. Kumar S, Ruiz N. Contact (Thousand Oaks) 6 25152564231185931 (2023)
  27. Gating of β-Barrel Protein Pores, Porins, and Channels: An Old Problem with New Facets. Mayse LA, Movileanu L. Int J Mol Sci 24 12095 (2023)
  28. Targeting LPS biosynthesis and transport in gram-negative bacteria in the era of multi-drug resistance. Romano KP, Hung DT. Biochim Biophys Acta Mol Cell Res 1870 119407 (2023)
  29. Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections. Theuretzbacher U, Blasco B, Duffey M, Piddock LJV. Nat Rev Drug Discov (2023)

Articles citing this publication (45)

  1. Thanatin targets the intermembrane protein complex required for lipopolysaccharide transport in Escherichia coli. Vetterli SU, Zerbe K, Müller M, Urfer M, Mondal M, Wang SY, Moehle K, Zerbe O, Vitale A, Pessi G, Eberl L, Wollscheid B, Robinson JA. Sci Adv 4 eaau2634 (2018)
  2. Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation. Riquelme SA, Liimatta K, Wong Fok Lung T, Fields B, Ahn D, Chen D, Lozano C, Sáenz Y, Uhlemann AC, Kahl BC, Britto CJ, DiMango E, Prince A. Cell Metab 31 1091-1106.e6 (2020)
  3. Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG. Luo Q, Yang X, Yu S, Shi H, Wang K, Xiao L, Zhu G, Sun C, Li T, Li D, Zhang X, Zhou M, Huang Y. Nat Struct Mol Biol 24 469-474 (2017)
  4. Phospholipid retention in the absence of asymmetry strengthens the outer membrane permeability barrier to last-resort antibiotics. Powers MJ, Trent MS. Proc Natl Acad Sci U S A 115 E8518-E8527 (2018)
  5. Murepavadin: a new antibiotic class in the pipeline. Martin-Loeches I, Dale GE, Torres A. Expert Rev Anti Infect Ther 16 259-268 (2018)
  6. The Crystal Structure of a Biological Insulated Transmembrane Molecular Wire. Edwards MJ, White GF, Butt JN, Richardson DJ, Clarke TA. Cell 181 665-673.e10 (2020)
  7. Structural and functional insights into the lipopolysaccharide ABC transporter LptB2FG. Dong H, Zhang Z, Tang X, Paterson NG, Dong C. Nat Commun 8 222 (2017)
  8. Lyme Disease in Humans. Radolf JD, Strle K, Lemieux JE, Strle F. Curr Issues Mol Biol 42 333-384 (2021)
  9. Disrupting Gram-Negative Bacterial Outer Membrane Biosynthesis through Inhibition of the Lipopolysaccharide Transporter MsbA. Alexander MK, Miu A, Oh A, Reichelt M, Ho H, Chalouni C, Labadie S, Wang L, Liang J, Nickerson NN, Hu H, Yu L, Du M, Yan D, Park S, Kim J, Xu M, Sellers BD, Purkey HE, Skelton NJ, Koehler MFT, Payandeh J, Verma V, Xu Y, Koth CM, Nishiyama M. Antimicrob Agents Chemother 62 e01142-18 (2018)
  10. Structural insights into outer membrane asymmetry maintenance in Gram-negative bacteria by MlaFEDB. Tang X, Chang S, Qiao W, Luo Q, Chen Y, Jia Z, Coleman J, Zhang K, Wang T, Zhang Z, Zhang C, Zhu X, Wei X, Dong C, Zhang X, Dong H. Nat Struct Mol Biol 28 81-91 (2021)
  11. Cryo-EM structures of lipopolysaccharide transporter LptB2FGC in lipopolysaccharide or AMP-PNP-bound states reveal its transport mechanism. Tang X, Chang S, Luo Q, Zhang Z, Qiao W, Xu C, Zhang C, Niu Y, Yang W, Wang T, Zhang Z, Zhu X, Wei X, Dong C, Zhang X, Dong H. Nat Commun 10 4175 (2019)
  12. Discovery of Novel Leptospirosis Vaccine Candidates Using Reverse and Structural Vaccinology. Grassmann AA, Grassmann AA, Kremer FS, Dos Santos JC, Souza JD, Pinto LDS, McBride AJA. Front Immunol 8 463 (2017)
  13. LetB Structure Reveals a Tunnel for Lipid Transport across the Bacterial Envelope. Isom GL, Coudray N, MacRae MR, McManus CT, Ekiert DC, Bhabha G. Cell 181 653-664.e19 (2020)
  14. Dynamics of an LPS translocon induced by substrate and an antimicrobial peptide. Fiorentino F, Sauer JB, Qiu X, Corey RA, Cassidy CK, Mynors-Wallis B, Mehmood S, Bolla JR, Stansfeld PJ, Robinson CV. Nat Chem Biol 17 187-195 (2021)
  15. Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses. Wach A, Dembowsky K, Dale GE. Antimicrob Agents Chemother 62 e02355-17 (2018)
  16. Mutation and Suppressor Analysis of the Essential Lipopolysaccharide Transport Protein LptA Reveals Strategies To Overcome Severe Outer Membrane Permeability Defects in Escherichia coli. Falchi FA, Maccagni EA, Puccio S, Peano C, De Castro C, Palmigiano A, Garozzo D, Martorana AM, Polissi A, Dehò G, Sperandeo P. J Bacteriol 200 e00487-17 (2018)
  17. Pseudomonas aeruginosa LptE is crucial for LptD assembly, cell envelope integrity, antibiotic resistance and virulence. Lo Sciuto A, Martorana AM, Fernández-Piñar R, Mancone C, Polissi A, Imperi F. Virulence 9 1718-1733 (2018)
  18. Massive antibody discovery used to probe structure-function relationships of the essential outer membrane protein LptD. Storek KM, Chan J, Vij R, Chiang N, Lin Z, Bevers J, Koth CM, Vernes JM, Meng YG, Yin J, Wallweber H, Dalmas O, Shriver S, Tam C, Schneider K, Seshasayee D, Nakamura G, Smith PA, Payandeh J, Koerber JT, Comps-Agrar L, Rutherford ST. Elife 8 e46258 (2019)
  19. Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter. Kaito C, Yoshikai H, Wakamatsu A, Miyashita A, Matsumoto Y, Fujiyuki T, Kato M, Ogura Y, Hayashi T, Isogai T, Sekimizu K. PLoS Pathog 16 e1008469 (2020)
  20. Characterizing Membrane Association and Periplasmic Transfer of Bacterial Lipoproteins through Molecular Dynamics Simulations. Rao S, Bates GT, Matthews CR, Newport TD, Vickery ON, Stansfeld PJ. Structure 28 475-487.e3 (2020)
  21. Structural Modeling of the Treponema pallidum Outer Membrane Protein Repertoire: a Road Map for Deconvolution of Syphilis Pathogenesis and Development of a Syphilis Vaccine. Hawley KL, Montezuma-Rusca JM, Delgado KN, Singh N, Uversky VN, Caimano MJ, Radolf JD, Luthra A. J Bacteriol 203 e0008221 (2021)
  22. Lipopolysaccharide Transport to the Cell Surface: New Insights in Assembly into the Outer Membrane. Sperandeo P, Polissi A. Structure 24 847-849 (2016)
  23. Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin. Zhou Y, Huang L, Ji S, Hou S, Luo L, Li C, Liu M, Liu Y, Jiang L. Molecules 24 E933 (2019)
  24. A pathway-directed positive growth restoration assay to facilitate the discovery of lipid A and fatty acid biosynthesis inhibitors in Acinetobacter baumannii. Richie DL, Wang L, Chan H, De Pascale G, Six DA, Wei JR, Dean CR. PLoS One 13 e0193851 (2018)
  25. Inward-facing glycine residues create sharp turns in β-barrel membrane proteins. Zhang Z, Ryoo D, Balusek C, Acharya A, Rydmark MO, Linke D, Gumbart JC. Biochim Biophys Acta Biomembr 1863 183662 (2021)
  26. Novel Small Molecule Growth Inhibitor Affecting Bacterial Outer Membrane Reduces Extraintestinal Pathogenic Escherichia coli (ExPEC) Infection in Avian Model. Kathayat D, Helmy YA, Deblais L, Srivastava V, Closs G, Khupse R, Rajashekara G. Microbiol Spectr 9 e0000621 (2021)
  27. Structure and Ligand-Binding Properties of the O Antigen ABC Transporter Carbohydrate-Binding Domain. Bi Y, Zimmer J. Structure 28 252-258.e2 (2020)
  28. Cryo-EM structures of a LptDE transporter in complex with Pro-macrobodies offer insight into lipopolysaccharide translocation. Botte M, Ni D, Schenck S, Zimmermann I, Chami M, Bocquet N, Egloff P, Bucher D, Trabuco M, Cheng RKY, Brunner JD, Seeger MA, Stahlberg H, Hennig M. Nat Commun 13 1826 (2022)
  29. Mutational analysis of the essential lipopolysaccharide-transport protein LptH of Pseudomonas aeruginosa to uncover critical oligomerization sites. Scala R, Di Matteo A, Coluccia A, Lo Sciuto A, Federici L, Travaglini-Allocatelli C, Visca P, Silvestri R, Imperi F. Sci Rep 10 11276 (2020)
  30. Degradation of Components of the Lpt Transenvelope Machinery Reveals LPS-Dependent Lpt Complex Stability in Escherichia coli. Martorana AM, Moura ECCM, Sperandeo P, Di Vincenzo F, Liang X, Toone E, Zhou P, Polissi A. Front Mol Biosci 8 758228 (2021)
  31. Designing of multi-epitope peptide vaccine against Acinetobacter baumannii through combined immunoinformatics and protein interaction-based approaches. Dey J, Mahapatra SR, Singh PK, Prabhuswamimath SC, Misra N, Suar M. Immunol Res 71 639-662 (2023)
  32. Gram-negative outer-membrane proteins with multiple β-barrel domains. Solan R, Pereira J, Lupas AN, Kolodny R, Ben-Tal N. Proc Natl Acad Sci U S A 118 e2104059118 (2021)
  33. Lipopolysaccharide Transport System Links Physiological Roles of σE and ArcA in the Cell Envelope Biogenesis in Shewanella oneidensis. Xie P, Liang H, Wang J, Huang Y, Gao H. Microbiol Spectr 9 e0069021 (2021)
  34. A Shaving Proteomic Approach to Unveil Surface Proteins Modulation of Multi-Drug Resistant Pseudomonas aeruginosa Strains Isolated From Cystic Fibrosis Patients. Montemari AL, Marzano V, Essa N, Levi Mortera S, Rossitto M, Gardini S, Selan L, Vrenna G, Onetti Muda A, Putignani L, Fiscarelli EV. Front Med (Lausanne) 9 818669 (2022)
  35. An investigation into the Omp85 protein BamK in hypervirulent Klebsiella pneumoniae, and its role in outer membrane biogenesis. Torres VVL, Heinz E, Stubenrauch CJ, Wilksch JJ, Cao H, Yang J, Clements A, Dunstan RA, Alcock F, Webb CT, Dougan G, Strugnell RA, Hay ID, Lithgow T. Mol Microbiol 109 584-599 (2018)
  36. Binding and transport of LPS occurs through the coordinated combination of an array of sites across the entire Escherichia coli LPS transport protein LptA. Schultz KM, Schneider JR, Fischer MA, Cina NP, Riegert MO, Frank DW, Klug CS. Protein Sci 32 e4724 (2023)
  37. Porins and Amyloids are Coded by Similar Sequence Motifs. Villain E, Nikekhin AA, Kajava AV. Proteomics 19 e1800075 (2019)
  38. Structure of an endogenous mycobacterial MCE lipid transporter. Chen J, Fruhauf A, Fan C, Ponce J, Ueberheide B, Bhabha G, Ekiert DC. Nature 620 445-452 (2023)
  39. Suppressor Mutations in LptF Bypass Essentiality of LptC by Forming a Six-Protein Transenvelope Bridge That Efficiently Transports Lipopolysaccharide. Falchi FA, Taylor RJ, Rowe SJ, Moura ECCM, Baeta T, Laguri C, Simorre JP, Kahne DE, Polissi A, Sperandeo P. mBio 14 e0220222 (2023)
  40. Categorization of Escherichia coli outer membrane proteins by dependence on accessory proteins of the β-barrel assembly machinery complex. Thewasano N, Germany EM, Maruno Y, Nakajima Y, Shiota T. J Biol Chem 299 104821 (2023)
  41. Cryo-EM reveals how the mastigoneme assembles and responds to environmental signal changes. Wang Y, Yang J, Hu F, Yang Y, Huang K, Zhang K. J Cell Biol 222 e202301066 (2023)
  42. Identification of a novel transport system in Borrelia burgdorferi that links the inner and outer membranes. Bowen HG, Kenedy MR, Johnson DK, MacKerell AD, Akins DR. Pathog Dis 81 ftad014 (2023)
  43. LptD depletion disrupts morphological homeostasis and upregulates carbohydrate metabolism in Escherichia coli. Frisinger FS, Jana B, Ortiz-Marquez JC, van Opijnen T, Donadio S, Guardabassi L. FEMS Microbes 4 xtad013 (2023)
  44. LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry. Yang Y, Chen H, Corey RA, Morales V, Quentin Y, Froment C, Caumont-Sarcos A, Albenne C, Burlet-Schiltz O, Ranava D, Stansfeld PJ, Marcoux J, Ieva R. Nat Commun 14 6368 (2023)
  45. Making a chink in their armor: Current and next-generation antimicrobial strategies against the bacterial cell envelope. Kadeřábková N, Mahmood AJS, Furniss RCD, Mavridou DAI. Adv Microb Physiol 83 221-307 (2023)