1932

Abstract

Single-molecule force spectroscopy (SMFS) has been widely applied to study the mechanical unfolding and folding of transmembrane proteins. Here, we review the recent progress in characterizing bacterial and human transmembrane β-barrel proteins by SMFS. First, we describe the mechanical unfolding of transmembrane β-barrels, which follows a general mechanism dictated by the sequential unfolding and extraction of individual β-strands and β-hairpins from membranes. Upon force relaxation, the unfolded polypeptide can insert stepwise into the membrane as single β-strands or β-hairpins to fold as the native β-barrel. The refolding can be followed at a high spatial and temporal resolution, showing that small β-barrels are able to fold without assistance, whereas large and complex β-barrels require chaperone cofactors. Applied in the dynamic mode, SMFS can quantify the kinetic and mechanical properties of single β-hairpins and reveal complementary insight into the membrane protein structure and function relationship. We further outline the challenges that SMFS experiments must overcome for a comprehensive understanding of the folding and function of transmembrane β-barrel proteins.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-anchem-061417-010055
2018-06-12
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/11/1/annurev-anchem-061417-010055.html?itemId=/content/journals/10.1146/annurev-anchem-061417-010055&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Lefkowitz RJ, Kobilka BK, Caron MG 1989. The new biology of drug receptors. Biochem. Pharmacol. 38:182941–48
    [Google Scholar]
  2. 2.  Yıldırım MA, Goh K-I, Cusick ME, Barabási A-L, Vidal M 2007. Drug–target network. Nat. Biotechnol. 25:101119–26
    [Google Scholar]
  3. 3.  Várady G, Cserepes J, Németh A, Szabó E, Sarkadi B 2013. Cell surface membrane proteins as personalized biomarkers: where we stand and where we are headed. Biomark. Med. 7:803–19
    [Google Scholar]
  4. 4.  Silhavy TJ, Kahne D, Walker S 2010. The bacterial cell envelope. Cold Spring Harb. Perspect. Biol. 2:51–16
    [Google Scholar]
  5. 5.  Nikaido H 2003. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev. 67:4593–656
    [Google Scholar]
  6. 6.  Pagès J-M, James CE, Winterhalter M 2008. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat. Rev. Microbiol. 6:12893–903
    [Google Scholar]
  7. 7.  Dowhan W, Bogdanov M 2002. Functional roles of lipids in membranes. New Compr. Biochem. 36:1–35
    [Google Scholar]
  8. 8.  Smit J, Kamio Y, Nikaido H 1975. Outer membrane of Salmonellatyphimurium: chemical analysis and freeze-fracture studies with lipopolysaccharide mutants. J. Bacteriol. 124:2942–58
    [Google Scholar]
  9. 9.  Kamio Y, Nikaido H 1976. Outer membrane of Salmonellatyphimurium: accessibility of phospholipid head groups to phospholipase C and cyanogen bromide activated dextran in the external medium. Biochemistry 15:122561–70
    [Google Scholar]
  10. 10.  Wallin E, von Heijne G 1998. Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms. Protein Sci 7:41029–38
    [Google Scholar]
  11. 11.  Wimley WC 2002. Toward genomic identification of β-barrel membrane proteins: composition and architecture of known structures. Protein Sci 11:2301–12
    [Google Scholar]
  12. 12.  Murzin A, Lesk A, Chothia C 1994. Principles determining the structure of β-sheet barrels in proteins I. A theoretical analysis. J. Mol. Biol. 236:51369–81
    [Google Scholar]
  13. 13.  Schulz GE 2002. The structure of bacterial outer membrane proteins. Biochim. Biophys. Acta 1565:2308–17
    [Google Scholar]
  14. 14.  Wimley WC 2003. The versatile β-barrel membrane protein. Curr. Opin. Struct. Biol. 13:4404–11
    [Google Scholar]
  15. 15.  Buchanan SK 1999. β-Barrel proteins from bacterial outer membranes: structure, function and refolding. Curr. Opin. Struct. Biol. 9:4455–61
    [Google Scholar]
  16. 16.  Koebnik R, Locher KP, Van Gelder P 2000. Structure and function of bacterial outer membrane proteins: barrels in a nutshell. Mol. Microbiol. 37:2239–53
    [Google Scholar]
  17. 17.  Rosenbusch JP 1988. Secondary and tertiary structure of membrane proteins. Zbl. Bakt. Suppl. 17:259–66
    [Google Scholar]
  18. 18.  Schulz GE 1992. Structure-function-relationships in the membrane channel porin as based on a 1.8 Ångstrom resolution crystal-structure. Membr. Proteins Struct. Interact. Model. 25:403–12
    [Google Scholar]
  19. 19.  Wülfing C, Plückthun A 1994. Protein folding in the periplasm of Escherichia coli. . Mol. Microbiol. 12:5685–92
    [Google Scholar]
  20. 20.  Nikaido H 1994. Porins and specific diffusion channels in bacterial outer membranes. J. Biol. Chem. 269:63905–8
    [Google Scholar]
  21. 21.  Ferguson A, Coulton J, Diederichs K, Welte W 2001. The ferric hydroxamate uptake receptor FhuA and related TonB-dependent transporters in the outer membrane of Gram-negative bacteria. Encyclopedia of Inorganic and Bioinorganic Chemistry RA Scott 834–49 Chichester, UK: John Wiley & Sons
    [Google Scholar]
  22. 22.  Moeck G, Coulton J 1998. TonB-dependent iron acquisition: mechanisms of siderophore-mediated active transport. Mol. Microbiol. 28:675–81
    [Google Scholar]
  23. 23.  Cowan SW, Schirmer T, Rummel G, Steiert M, Ghosh R et al. 1992. Crystal structures explain functional properties of two E. coli porins. Nature 358:6389727–33
    [Google Scholar]
  24. 24.  Masi M, Pagès J 2013. Structure, function and regulation of outer membrane proteins involved in drug transport in Enterobactericeae: the OmpF/C-TolC case. Open Microbiol. J. 7:22–33
    [Google Scholar]
  25. 25.  Luckey M, Nikaido H 1980. Specificity of diffusion channels produced by lambda phage receptor protein of Escherichia coli. . PNAS 77:1167–71
    [Google Scholar]
  26. 26.  Ranquin A, Van Gelder P 2004. Maltoporin: sugar for physics and biology. Res. Microbiol. 155:8611–16
    [Google Scholar]
  27. 27.  Killmann H, Benz R, Braun V 1993. Conversion of the FhuA transport protein into a diffusion channel through the outer membrane of Escherichia coli. . EMBO J 12:83007–16
    [Google Scholar]
  28. 28.  Locher KP, Rees B, Koebnik R, Mitschler A, Moulinier L et al. 1998. Transmembrane signaling across the ligand-gated FhuA receptor: crystal structures of free and ferrichrome-bound states reveal allosteric changes. Cell 95:6771–78
    [Google Scholar]
  29. 29.  Ferguson AD, Hofmann E, Coulton JW, Diederichs K, Welte W 1998. Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide. Science 282:53972215–20
    [Google Scholar]
  30. 30.  Pawelek PD, Croteau N, Ng-Thow-Hing C, Khursigara CM, Moiseeva N et al. 2006. Structure of TonB in complex with FhuA, E. coli outer membrane receptor. Science 312:57781399–1402
    [Google Scholar]
  31. 31.  Smith SGJ, Mahon V, Lambert MA, Fagan RP 2007. A molecular Swiss army knife: OmpA structure, function and expression. FEMS Microbiol. Lett. 273:11–11
    [Google Scholar]
  32. 32.  Wang Y 2002. The function of OmpA in Escherichia coli. . Biochem. Biophys. Res. Commun. 292:2396–401
    [Google Scholar]
  33. 33.  Mecsas J, Welch R, Erickson JW, Gross CA 1995. Identification and characterization of an outer membrane protein, OmpX, in Escherichia coli that is homologous to a family of outer membrane proteins including Ail of Yersiniaenterocolitica. . J. Bacteriol. 177:3799–804
    [Google Scholar]
  34. 34.  May KL, Silhavy TJ 2016. Making a membrane on the other side of the wall. Biochim. Biophys. Acta 1862:111386–93
    [Google Scholar]
  35. 35.  Hagan CL, Silhavy TJ, Kahne D 2011. β-Barrel membrane protein assembly by the Bam complex. Annu. Rev. Biochem. 80:189–210
    [Google Scholar]
  36. 36.  Knowles TJ, Scott-Tucker A, Overduin M, Henderson IR 2009. Membrane protein architects: the role of the BAM complex in outer membrane protein assembly. Nat. Rev. Microbiol. 7:3206–14
    [Google Scholar]
  37. 37.  Rollauer SE, Sooreshjani MA, Noinaj N, Buchanan SK 2015. Outer membrane protein biogenesis in Gram-negative bacteria. Philos. Trans. R. Soc. B 370:167920150023
    [Google Scholar]
  38. 38.  Selkrig J, Leyton DL, Webb CT, Lithgow T 2014. Assembly of β-barrel proteins into bacterial outer membranes. Biochim. Biophys. Acta 1843:81542–50
    [Google Scholar]
  39. 39.  Sperandeo P, Lau FK, Carpentieri A, De Castro C, Molinaro A et al. 2008. Functional analysis of the protein machinery required for transport of lipopolysaccharide to the outer membrane of Escherichia coli. . J. Bacteriol. 190:134460–69
    [Google Scholar]
  40. 40.  Haarmann R, Ibrahim M, Stevanovic M, Bredemeier R, Schleiff E 2010. The properties of the outer membrane localized Lipid A transporter LptD. J. Phys. Condens. Matter 22:45454124
    [Google Scholar]
  41. 41.  Costa TRD, Felisberto-Rodrigues C, Meir A, Prevost MS, Redzej A et al. 2015. Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat. Rev. Microbiol. 13:6343–59
    [Google Scholar]
  42. 42.  Mühlradt PF, Menzel J, Golecki JR, Speth V 1974. Lateral mobility and surface density of lipopolysaccharide in the outer membrane of Salmonellatyphimurium. . Eur. J. Biochem. 43:533–39
    [Google Scholar]
  43. 43.  Aldea M, Herrero E, Esteve MI, Guerrero R 1980. Surface density of major outer membrane proteins in Salmonellatyphimurium in different growth conditions. J. Gen. Microbiol. 120:2355–67
    [Google Scholar]
  44. 44.  Hall M, Silhavy T 1981. Genetic analysis of the major outer membrane proteins of Escherichia coli. . Annu. Rev. Genet. 15:91–142
    [Google Scholar]
  45. 45.  Sagan L 1967. On the origin of mitosing cells. J. Theor. Biol. 14:3225–74
    [Google Scholar]
  46. 46.  Zeth K 2010. Structure and evolution of mitochondrial outer membrane proteins of β-barrel topology. Biochim. Biophys. Acta 1797:6–71292–99
    [Google Scholar]
  47. 47.  Cavalier-Smith T 2000. Membrane heredity and early chloroplast evolution. Trends Plant Sci 5:4174–82
    [Google Scholar]
  48. 48.  Duncan O, van der Merwe MJ, Daley DO, Whelan J 2013. The outer mitochondrial membrane in higher plants. Trends Plant Sci 18:4207–17
    [Google Scholar]
  49. 49.  Höhr AIC, Straub SP, Warscheid B, Becker T, Wiedemann N 2015. Assembly of β-barrel proteins in the mitochondrial outer membrane. Biochim. Biophys. Acta Mol. Cell Res. 1853:174–88
    [Google Scholar]
  50. 50.  Webb CT, Heinz E, Lithgow T 2012. Evolution of the β-barrel assembly machinery. Trends Microbiol 20:12612–20
    [Google Scholar]
  51. 51.  Mannella CA 1992. The “ins” and “outs” of mitochondrial membrane channels. Trends Biochem. Sci. 17:8315–20
    [Google Scholar]
  52. 52.  Benz R 1994. Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins. Biochim. Biophys. Acta Rev. Biomembr. 1197:2167–96
    [Google Scholar]
  53. 53.  Gerber C, Lang HP 2008. How the doors to the nanoworld were opened. Nat. Nanotechnol. 1:13–5
    [Google Scholar]
  54. 54.  Müller DJ, Dufrêne YF 2008. Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology. Nat. Nanotechnol. 3:5261–69
    [Google Scholar]
  55. 55.  Dufrêne YF, Ando T, Garcia R, Alsteens D, Martinez-Martin D et al. 2017. Imaging modes of atomic force microscopy for application in molecular and cell biology. Nat. Nanotechnol. 12:4295–307
    [Google Scholar]
  56. 56.  Müller DJ, Schabert FA, Büldt G, Engel A 1995. Imaging purple membranes in aqueous solutions at sub-nanometer resolution by atomic force microscopy. Biophys. J. 68:51681–86
    [Google Scholar]
  57. 57.  Engel A, Gaub HE 2008. Structure and mechanics of membrane proteins. Annu. Rev. Biochem. 77:127–48
    [Google Scholar]
  58. 58.  Oesterhelt F, Oesterhelt D, Pfeiffer M, Engel A, Gaub HE, Müller DJ 2000. Unfolding pathways of individual bacteriorhodopsins. Science 288:5463143–46
    [Google Scholar]
  59. 59.  Fotiadis D, Müller DJ, Tsiotis G, Hasler L, Tittmann P et al. 1998. Surface analysis of the photosystem I complex by electron and atomic force microscopy. J. Mol. Biol. 283:83–94
    [Google Scholar]
  60. 60.  Müller DJ, Büldt G, Engel A 1995. Force-induced conformational change of bacteriorhodopsin. J. Mol. Biol. 249:239–43
    [Google Scholar]
  61. 61.  Marko JF, Siggia ED 1995. Stretching DNA. Macromolecules 28:268759–70
    [Google Scholar]
  62. 62.  Rief M, Oesterhelt F, Heymann B, Gaub HE 1997. Single molecule force spectroscopy on polysaccharides by atomic force microscopy. Science 275:53041295–97
    [Google Scholar]
  63. 63.  Oberhauser AF, Marszalek PE, Erickson HP, Fernandez JM 1998. The molecular elasticity of the extracellular matrix protein tenascin. Nature 393:6681181–85
    [Google Scholar]
  64. 64.  Kedrov A, Janovjak H, Sapra KT, Müller DJ 2007. Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy. Annu. Rev. Biophys. Biomol. Struct. 36:Jan.233–60
    [Google Scholar]
  65. 65.  Borgia A, Williams PM, Clarke J 2008. Single-molecule studies of protein folding. Annu. Rev. Biochem. 77:101–25
    [Google Scholar]
  66. 66.  Clausen-Schaumann H, Seitz M, Krautbauer R, Gaub HE 2000. Force spectroscopy with single bio-molecules. Curr. Opin. Chem. Biol. 4:5524–30
    [Google Scholar]
  67. 67.  Müller DJ, Engel A 2007. Atomic force microscopy and spectroscopy of native membrane proteins. Nat. Protoc. 2:92191–97
    [Google Scholar]
  68. 68.  Butt HJ, Jaschke M 1995. Calculation of thermal noise in atomic force microscopy. Nanotechnology 6:1–7
    [Google Scholar]
  69. 69.  Bustamante C, Marko J, Siggia ED, Smith S 1994. Entropic elasticity of λ-phage DNA. Science 265:51785–6
    [Google Scholar]
  70. 70.  Janovjak H, Knaus H, Muller DJ 2007. Transmembrane helices have rough energy surfaces. J. Am. Chem. Soc. 129:2246–47
    [Google Scholar]
  71. 71.  Fajardo DA, Cheung J, Ito C, Sugawara E, Nikaido H, Misra R 1998. Biochemistry and regulation of a novel Escherichia coli K-12 porin protein, OmpG, which produces unusually large channels. J. Bacteriol. 180:174452–59
    [Google Scholar]
  72. 72.  Conlan S, Zhang Y, Cheley S, Bayley H 2000. Biochemical and biophysical characterization of OmpG: a monomeric porin. Biochemistry 39:3911845–54
    [Google Scholar]
  73. 73.  Yildiz Ö, Vinothkumar KR, Goswami P, Kühlbrandt W 2006. Structure of the monomeric outer-membrane porin OmpG in the open and closed conformation. EMBO J 25:153702–13
    [Google Scholar]
  74. 74.  Misra R, Benson SA 1989. A novel mutation, cog, which results in production of a new porin protein (OmpG) of Escherichia coli K-12. J. Bacteriol. 171:84105–11
    [Google Scholar]
  75. 75.  Subbarao GV, van den Berg B 2006. Crystal structure of the monomeric porin OmpG. J. Mol. Biol. 360:4750–59
    [Google Scholar]
  76. 76.  Liang B, Tamm LK 2007. Structure of outer membrane protein G by solution NMR spectroscopy. PNAS 104:4116140–45
    [Google Scholar]
  77. 77.  Sapra KT, Damaghi M, Köster S, Yildiz Ö, Kühlbrandt W, Muller DJ 2009. One β hairpin after the other: exploring mechanical unfolding pathways of the transmembrane β-barrel protein OmpG. Angew. Chem. Int. Ed. 48:448306–8
    [Google Scholar]
  78. 78.  Damaghi M, Bippes C, Köster S, Yildiz Ö, Mari SA et al. 2010. pH-dependent interactions guide the folding and gate the transmembrane pore of the β-barrel membrane protein OmpG. J. Mol. Biol. 397:4878–82
    [Google Scholar]
  79. 79.  Damaghi M, Sapra KT, Köster S, Yildiz Ö, Kühlbrandt W, Muller DJ 2010. Dual energy landscape: the functional state of the β-barrel outer membrane protein G molds its unfolding energy landscape. Proteomics 10:234151–62
    [Google Scholar]
  80. 80.  Hensen U, Müller DJ 2013. Mechanistic explanation of different unfolding behaviors observed for transmembrane and soluble β-barrel proteins. Structure 21:81317–24
    [Google Scholar]
  81. 81.  Gräter F, Shen J, Jiang H, Gautel M, Grubmüller H 2005. Mechanically induced titin kinase activation studied by force-probe molecular dynamics simulations. Biophys. J. 88:2790–804
    [Google Scholar]
  82. 82.  Park JS, Lee WC, Yeo KJ, Ryu K-S, Kumarasiri M et al. 2012. Mechanism of anchoring of OmpA protein to the cell wall peptidoglycan of the gram-negative bacterial outer membrane. FASEB J 26:1219–28
    [Google Scholar]
  83. 83.  Renault M, Saurel O, Czaplicki J, Demange P, Gervais V et al. 2009. Solution state NMR structure and dynamics of KpOmpA, a 210 residue transmembrane domain possessing a high potential for immunological applications. J. Mol. Biol. 385:1117–30
    [Google Scholar]
  84. 84.  Pautsch A, Schulz GE 1998. Structure of the outer membrane protein A transmembrane domain. Nat. Struct. Biol. 5:111013–17
    [Google Scholar]
  85. 85.  Jeannin P, Renno T, Goetsch L, Miconnet I, Aubry JP et al. 2000. OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway. Nat. Immunol. 1:6502–9
    [Google Scholar]
  86. 86.  Soulas C, Baussant T, Aubry JP, Delneste Y, Barillat N et al. 2000. Cutting edge: outer membrane protein A (OmpA) binds to and activates human macrophages. J. Immunol. 165:52335–40
    [Google Scholar]
  87. 87.  Bosshart PD, Iordanov I, Garzon-Coral C, Demange P, Engel A et al. 2012. The transmembrane protein KpOmpA anchoring the outer membrane of Klebsiellapneumoniae unfolds and refolds in response to tensile load. Structure 20:1121–27
    [Google Scholar]
  88. 88.  Schirmer T, Keller TA, Wang Y, Rosenbusch JP 1995. Structural basis for sugar translocation through maltoporin channels at 3.1 Å resolution. Science 267:5197512–14
    [Google Scholar]
  89. 89.  Dutzler R, Wang YF, Rizkallah P, Rosenbusch J, Schirmer T 1996. Crystal structures of various maltooligosaccharides bound to maltoporin reveal a specific sugar translocation pathway. Structure 4:2127–34
    [Google Scholar]
  90. 90.  Van Gelder P Dumas F, Bartoldus I, Saint N, Prilipov A et al. 2002. Sugar transport through maltoporin of Escherichia coli: role of the greasy slide. J. Bacteriol. 184:112994–99
    [Google Scholar]
  91. 91.  Neilands JB 1982. Microbial envelope proteins related to iron. Annu. Rev. Microbiol. 36:285–309
    [Google Scholar]
  92. 92.  Moeck GS, Coulton JW, Postle K 1997. Cell envelope signaling in Escherichia coli ligand binding to the ferrichrome-iron receptor FhuA promotes interaction with the energy-transducing protein TonB. J. Biol. Chem. 272:4528391–97
    [Google Scholar]
  93. 93.  Thoma J, Bosshart P, Pfreundschuh M, Müller DJ 2012. Out but not in: the large transmembrane β-barrel protein FhuA unfolds but cannot refold via β-hairpins. Structure 20:122185–90
    [Google Scholar]
  94. 94.  Hiller S, Garces RG, Malia TJ, Orekhov VY, Colombini M, Wagner G 2008. Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science 321:1206–10
    [Google Scholar]
  95. 95.  Bayrhuber M, Meins T, Habeck M, Becker S, Giller K et al. 2008. Structure of the human voltage-dependent anion channel. PNAS 105:4015370–75
    [Google Scholar]
  96. 96.  Ge L, Villinger S, Mari SA, Giller K, Griesinger C et al. 2016. Molecular plasticity of the human voltage-dependent anion channel embedded into a membrane. Structure 24:4585–94
    [Google Scholar]
  97. 97.  Evans EA, Calderwood DA 2007. Forces and bond dynamics in cell adhesion. Science 316:58281148–53
    [Google Scholar]
  98. 98.  Evans E, Ritchie K 1997. Dynamic strength of molecular adhesion bonds. Biophys. J. 72:41541–55
    [Google Scholar]
  99. 99.  Bowie JU 2005. Solving the membrane protein folding problem. Nature 438:7068581–89
    [Google Scholar]
  100. 100.  Harris NJ, Booth PJ 2012. Folding and stability of membrane transport proteins in vitro. . Biochim. Biophys. Acta Biomembr. 1818:41055–66
    [Google Scholar]
  101. 101.  Damaghi M, Köster S, Bippes CA, Yildiz Ö, Müller DJ 2011. One β hairpin follows the other: exploring refolding pathways and kinetics of the transmembrane β-barrel protein OmpG. Angew. Chem. Int. Ed. 50:327422–24
    [Google Scholar]
  102. 102.  Thoma J, Burmann BM, Hiller S, Müller DJ 2015. Impact of holdase chaperones Skp and SurA on the folding of β-barrel outer-membrane proteins. Nat. Struct. Mol. Biol. 22:10795–802
    [Google Scholar]
  103. 103.  Serdiuk T, Balasubramaniam D, Sugihara J, Mari SA, Kaback HR, Müller DJ 2016. YidC assists the stepwise and stochastic folding of membrane proteins. Nat. Chem. Biol. 12:11911–17
    [Google Scholar]
  104. 104.  Serdiuk T, Mari SA, Müller DJ 2017. Pull-and-paste of single transmembrane proteins. Nano Lett 17:74478–88
    [Google Scholar]
  105. 105.  Yu H, Siewny MGW, Edwards DT, Sanders AW, Perkins TT 2017. Hidden dynamics in the unfolding of individual bacteriorhodopsin proteins. Science 355:6328945–50
    [Google Scholar]
  106. 106.  Petrosyan R, Bippes CA, Walheim S, Harder D, Fotiadis D et al. 2015. Single-molecule force spectroscopy of membrane proteins from membranes freely spanning across nanoscopic pores. Nano Lett 15:53624–33
    [Google Scholar]
  107. 107.  Marcoux J, Politis A, Rinehart D, Marshall DP, Wallace MI et al. 2014. Mass spectrometry defines the C-terminal dimerization domain and enables modeling of the structure of full-length OmpA. Structure 22:5781–90
    [Google Scholar]
/content/journals/10.1146/annurev-anchem-061417-010055
Loading
/content/journals/10.1146/annurev-anchem-061417-010055
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error