Skip to main content
SpringerLink
Log in
Book cover

International Conference on Pure and Applied Chemistry

ICPAC 2018: Chemistry for a Clean and Healthy Planet pp 71–83Cite as

The Molecular Dynamics Simulation of a Multi-domain Outer Membrane Protein A (OmpA) from Shigella flexneri in POPE Lipid Bilayer

  • Conference paper
  • First Online:

  • 527 Accesses

Abstract

Shigella flexneri serotype 2a is a major public health concern in the developing and under-developed countries as it contributes to the endemic shigellosis (also known as bacillus dysentery) as well as shigellosis mortality. A 35 kDa antigenic protein from S. flexneri has been shown to be a potential biomarker and the predictive model from earlier studies showed that this protein is a variant of outer membrane protein A (OmpA) that consists of OmpA domain and OmpA-like domain. This study was conducted to further sample and explore the conformation of the OmpA of S. flexneri in POPE lipid bilayer. The trajectories data from molecular dynamics (MD) simulation showed that the OmpA secondary structure is retained and the protein integrity is not impaired. The four extracellular loops are flexible and similar observation was noted for the linker of the two domains. The conformation of the extracellular loops could be useful for possible future development for diagnostics or vaccine of shigellosis.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Camacho AI, Irache JM, de Souza J, Sanchez-Gomez S, Gamazo C (2013) Nanoparticle-based vaccine for mucosal protection against Shigella flexneri in mice. Vaccine 31:3288–3294

    Article  CAS  PubMed  Google Scholar 

  2. Kotloff KL, Winickoff JP, Ivanoff B, Clemens JD, Swerdlow DL, Sansonetti PJ, Adak GK, Levine MM (1999) Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ 77:651–666

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Jennison AV, Verma NK (2004) Shigella flexneri infection: pathogenesis and vaccine development. FEMS Microbiol Rev 28:43–58

    Article  CAS  PubMed  Google Scholar 

  4. Liu J, Platts-Mills JA, Juma J, Kabir F, Nkeze J, Okoi C, Operario DJ, Uddin J, Ahmed S, Alonso PL, Antonio M, Becker SM, Blackwelder WC, Breiman RF, Faruque AS, Fields B, Gratz J, Haque R, Hossain A, Hossain MJ, Jarju S, Qamar F, Iqbal NT, Kwambana B, Mandomando I, McMurry TL, Ochieng C, Ochieng JB, Ochieng M, Onyango C, Panchalingam S, Kalam A, Aziz F, Qureshi S, Ramamurthy T, Roberts JH, Saha D, Sow SO, Stroup SE, Sur D, Tamboura B, Taniuchi M, Tennant SM, Toema D, Wu Y, Zaidi A, Nataro JP, Kotloff KL, Levine MM, Houpt ER (2016) Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet 388:1291–1301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pires SM, Fischer-Walker CL, Lanata CF, Devleesschauwer B, Hall AJ, Kirk MD, Duarte AS, Black RE, Angulo FJ (2015) Aetiology-specific estimates of the global and regional incidence and mortality of diarrhoeal diseases commonly transmitted through food. PLoS ONE 10:e0142927

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zaidi MB, Estrada-Garcia T (2014) Shigella: a highly virulent and elusive pathogen. Curr Trop Med Rep 1:81–87

    PubMed  PubMed Central  Google Scholar 

  7. Ambrosi C, Pompili M, Scribano D, Zagaglia C, Ripa S, Nicoletti M (2012) Outer membrane protein A (OmpA): a new player in Shigella flexneri protrusion formation and inter-cellular spreading. PLoS ONE 7:e49625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Confer AW, Ayalew S (2013) The OmpA family of proteins: roles in bacterial pathogenesis and immunity. Vet Microbiol 163:207–222

    Article  CAS  PubMed  Google Scholar 

  9. Pore D, Chakrabarti MK (2013) Outer membrane protein A (OmpA) from Shigella flexneri 2a: a promising subunit vaccine candidate. Vaccine 31:3644–3650

    Article  CAS  PubMed  Google Scholar 

  10. Biggin PC, Bond PJ (2008) Molecular dynamics simulations of membrane proteins. Methods Mol Biol 443:147–160

    Article  CAS  PubMed  Google Scholar 

  11. Domene C, Bond PJ, Sansom MS (2003) Membrane protein simulations: ion channels and bacterial outer membrane proteins. Adv Protein Chem 66:159–193

    Article  CAS  PubMed  Google Scholar 

  12. Dror RO, Jensen MO, Shaw DE (2009) Elucidating membrane protein function through long-timescale molecular dynamics simulation. Conf Proc IEEE Eng Med Biol Soc 2009:2340–2342

    Google Scholar 

  13. Gumbart J, Wang Y, Aksimentiev A, Tajkhorshid E, Schulten K (2005) Molecular dynamics simulations of proteins in lipid bilayers. Curr Opin Struct Biol 15:423–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lindahl E, Sansom MS (2008) Membrane proteins: molecular dynamics simulations. Curr Opin Struct Biol 18:425–431

    Article  CAS  PubMed  Google Scholar 

  15. Khalid S, Bond PJ, Carpenter T, Sansom MS (2008) OmpA: gating and dynamics via molecular dynamics simulations. Biochim Biophys Acta 1778:1871–1880

    Article  CAS  PubMed  Google Scholar 

  16. Straatsma TP, Soares TA (2009) Characterization of the outer membrane protein OprF of Pseudomonas aeruginosa in a lipopolysaccharide membrane by computer simulation. Proteins 74:475–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tieleman DP, Berendsen HJ (1998) A molecular dynamics study of the pores formed by Escherichia coli OmpF porin in a fully hydrated palmitoyl oleoyl phosphatidylcholine bilayer. Biophys J 74:2786–2801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. DeChancie J, Shrivastava IH, Bahar I (2011) The mechanism of substrate release by the aspartate transporter GltPh: insights from simulations. Mol BioSyst 7:832–842

    Article  CAS  PubMed  Google Scholar 

  19. Khalili-Araghi F, Gumbart J, Wen PC, Sotomayor M, Tajkhorshid E, Schulten K (2009) Molecular dynamics simulations of membrane channels and transporters. Curr Opin Struct Biol 19:128–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shi L, Weinstein H (2010) Conformational rearrangements to the intracellular open states of the LeuT and ApcT transporters are modulated by common mechanisms. Biophys J 99:L103–L105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hub JS, Grubmuller H, de Groot BL (2009) Dynamics and energetics of permeation through aquaporins. What do we learn from molecular dynamics simulations? Handb Exp Pharmacol 57–76

    Google Scholar 

  22. Qiu H, Ma S, Shen R, Guo W (2010) Dynamic and energetic mechanisms for the distinct permeation rate in AQP1 and AQP0. Biochim Biophys Acta 1798:318–326

    Article  CAS  PubMed  Google Scholar 

  23. Wang Y, Schulten K, Tajkhorshid E (2005) What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF. Structure 13:1107–1118

    Article  CAS  PubMed  Google Scholar 

  24. Yung-Hung RL, Ismail A, Lim TS, Choong YS (2011) A 35 kDa antigenic protein from Shigella flexneri: in silico structural and functional studies. Biochem Biophys Res Commun 415:229–234

    Article  CAS  PubMed  Google Scholar 

  25. De Mot R, Vanderleyden J (1994) The C-terminal sequence conservation between OmpA-related outer membrane proteins and MotB suggests a common function in both gram-positive and gram-negative bacteria, possibly in the interaction of these domains with peptidoglycan. Mol Microbiol 12:333–334

    Article  PubMed  Google Scholar 

  26. Holtje JV (1998) Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli. Microbiol Mol Biol Rev 62:181–203

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Koebnik R (1995) Proposal for a peptidoglycan-associating alpha-helical motif in the C-terminal regions of some bacterial cell-surface proteins. Mol Microbiol 16:1269–1270

    Article  CAS  PubMed  Google Scholar 

  28. Ortiz-Suarez ML, Samsudin F, Piggot TJ, Bond PJ, Khalid S (2016) Full-length OmpA: structure, function, and membrane interactions predicted by molecular dynamics simulations. Biophys J 111:1692–1702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schiffrin B, Brockwell DJ, Radford SE (2017) Outer membrane protein folding from an energy landscape perspective. BMC Biol 15:123

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4:435–447

    Article  CAS  PubMed  Google Scholar 

  31. Stansfeld PJ, Sansom MS (2011) Molecular simulation approaches to membrane proteins. Structure 19:1562–1572

    Article  CAS  PubMed  Google Scholar 

  32. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935

    Article  CAS  Google Scholar 

  33. Darden T, York D, Pedersen L (1993) Particle mesh Ewald: An Nâ‹…log(N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  34. Berendsen HJC, Postma JPM, Vangunsteren WF, Dinola A, Haak JR (1984) Molecular-dynamics with coupling to an external bath. J Chem Phys 81:3684–3690

    Article  CAS  Google Scholar 

  35. Hoover WG (1985) Canonical dynamics: equilibrium phase-space distributions. Phys Rev A 31:1695–1697

    Article  CAS  Google Scholar 

  36. Best RB, Zhu X, Shim J, Lopes PE, Mittal J, Feig M, MacKerell AD Jr (2012) Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone phi, psi and side-chain chi(1) and chi(2) dihedral angles. J Chem Theory Comput 8:3257–3273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Huang J, MacKerell AD Jr (2013) CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data. J Comput Chem 34:2135–2145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM (1997) LINCS: a linear constraint solver for molecular simulations. J Comput Chem 18:1463–1472

    Article  CAS  Google Scholar 

  39. Miyamoto S, Kollman PA (1992) SETTLE: an analytical version of the SHAKE and RATTLE algorithm for rigid water models. J Comput Chem 13:952–962

    Article  CAS  Google Scholar 

  40. Wolf A, Kirschner KN (2013) Principal component and clustering analysis on molecular dynamics data of the ribosomal L11.23S subdomain. J Mol Model 19:539–549

    Article  CAS  PubMed  Google Scholar 

  41. Smart OS, Neduvelil JG, Wang X, Wallace BA, Sansom MS (1996) HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J Mol Graph 14:354–360

    Article  CAS  PubMed  Google Scholar 

  42. Lobanov M, Bogatyreva NS, Galzitskaia OV (2008) Radius of gyration is indicator of compactness of protein structure. Mol Biol 42:701–706

    Article  Google Scholar 

  43. Schwede T (2013) Protein modeling: what happened to the “protein structure gap”? Structure 21:1531–1540

    Article  CAS  PubMed  Google Scholar 

  44. Roux B (2005) Ion conduction and selectivity in K(+) channels. Annu Rev Biophys Biomol Struct 34:153–171

    Article  CAS  PubMed  Google Scholar 

  45. Ruiz N, Kahne D, Silhavy TJ (2006) Advances in understanding bacterial outer-membrane biogenesis. Nature Rev Microbiol 4:57–66

    Article  Google Scholar 

  46. Carpenter T, Khalid S, Sansom MS (2007) A multidomain outer membrane protein from Pasteurella multocida: modelling and simulation studies of PmOmpA. Biochim Biophys Acta 1768:2831–2840

    Article  CAS  PubMed  Google Scholar 

  47. Hwang PM, Choy WY, Lo EI, Chen L, Forman-Kay JD, Raetz CR, Prive GG, Bishop RE, Kay LE (2002) Solution structure and dynamics of the outer membrane enzyme PagP by NMR. Proc Natl Acad Sci USA 99:13560–13565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Fernandez C, Hilty C, Wider G, Guntert P, Wuthrich K (2004) NMR structure of the integral membrane protein OmpX. J Mol Biol 336:1211–1221

    Article  CAS  PubMed  Google Scholar 

  49. Mushtaq AU, Park JS, Bae SH, Kim HY, Yeo KJ, Hwang E, Lee KY, Jee JG, Cheong HK, Jeon YH (2017) Ligand-mediated folding of the OmpA periplasmic domain from Acinetobacter baumannii. Biophys J 112:2089–2098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Freudl R (1989) Insertion of peptides into cell-surface-exposed areas of the Escherichia coli OmpA protein does not interfere with export and membrane assembly. Gene 82:229–236

    Article  CAS  PubMed  Google Scholar 

  51. Bessette PH, Hu X, Soh HT, Daugherty PS (2007) Microfluidic library screening for mapping antibody epitopes. Anal Chem 79:2174–2178

    Article  CAS  PubMed  Google Scholar 

  52. Bessette PH, Rice JJ, Daugherty PS (2004) Rapid isolation of high-affinity protein binding peptides using bacterial display. Protein Eng Des Sel 17:731–739

    Article  CAS  PubMed  Google Scholar 

  53. Ruppert A, Arnold N, Hobom G (1994) OmpA-FMDV VP1 fusion proteins: production, cell surface exposure and immune responses to the major antigenic domain of foot-and-mouth disease virus. Vaccine 12:492–498

    Article  CAS  PubMed  Google Scholar 

  54. Mejare M, Ljung S, Bulow L (1998) Selection of cadmium specific hexapeptides and their expression as OmpA fusion proteins in Escherichia coli. Protein Eng 11:489–494

    Article  CAS  PubMed  Google Scholar 

  55. Camaj P, Hirsh AE, Schmidt W, Meinke A, von Gabain A (2001) Ligand-mediated protection against phage lysis as a positive selection strategy for the enrichment of epitopes displayed on the surface of E. coli cells. Biol Chem 382:1669–1677

    Article  CAS  PubMed  Google Scholar 

  56. Bond PJ, Faraldo-Gomez JD, Sansom MS (2002) OmpA: a pore or not a pore? Simulation and modeling studies. Biophys J 83:763–775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hong H, Szabo G, Tamm LK (2006) Electrostatic couplings in OmpA ion-channel gating suggest a mechanism for pore opening. Nat Chem Biol 2:627–635

    Article  CAS  PubMed  Google Scholar 

  58. Brinkman FS, Bains M, Hancock RE (2000) The amino terminus of Pseudomonas aeruginosa outer membrane protein OprF forms channels in lipid bilayer membranes: correlation with a three-dimensional model. J Bacteriol 182:5251–5255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Arora A, Abildgaard F, Bushweller JH, Tamm LK (2001) Structure of outer membrane protein A transmembrane domain by NMR spectroscopy. Nat Struct Biol 8:334–338

    Article  CAS  PubMed  Google Scholar 

  60. Hub JS, de Groot BL (2008) Mechanism of selectivity in aquaporins and aquaglyceroporins. Proc Natl Acad Sci USA 105:1198–1203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Krishnan S, Liu F, Abrol R, Hodges J, Goddard WA 3rd, Prasadarao NV (2014) The interaction of N-glycans in Fcgamma receptor I alpha-chain with Escherichia coli K1 outer membrane protein A for entry into macrophages: experimental and computational analysis. J Biol Chem 289:30937–30949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was funded by Universiti Sains Malaysia (USM) Research University Grant (1001/CIPPM/811051) and Bridging Grant (304/CIPPM/6316018). The computational resources were provided by Higher Institutions Centre of Excellence (HICoE) Grant (311/CIPPM/44001005) from the Malaysia Ministry of Education. Thanks also to Universiti Sains Malaysia Fellowship and Malaysia Ministry of Higher Education MyBrain scholarship for RL Yung-Hung.

Author information

Authors and Affiliations

  1. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800, Penang, Malaysia

    Roy Lee Yung-Hung, Theam Soon Lim & Yee Siew Choong

  2. Institute for Research in Molecular Medicine, Health Campus, Universiti Sains Malaysia, 16150, Kubang Kerian, Malaysia

    Asma Ismail

Authors
  1. Roy Lee Yung-Hung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theam Soon Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Asma Ismail
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yee Siew Choong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yee Siew Choong .

Editor information

Editors and Affiliations

  1. Department of Chemistry, Faculty of Science, University of Mauritius, Reduit, Mauritius

    Ponnadurai Ramasami

  2. Dept of Chemistry, Faculty of Scien, University of Mauritius, Reduit, Mauritius

    Minu Gupta Bhowon

  3. Dept. of Chemistry, Faculty of Scie, University of Mauritius, Reduit, Mauritius

    Sabina Jhaumeer Laulloo

  4. Dept. of Chem., Fac. of Science, University of Mauritius, Reduit, Mauritius

    Henri Li Kam Wah

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Yung-Hung, R.L., Lim, T.S., Ismail, A., Choong, Y.S. (2019). The Molecular Dynamics Simulation of a Multi-domain Outer Membrane Protein A (OmpA) from Shigella flexneri in POPE Lipid Bilayer. In: Ramasami, P., Gupta Bhowon, M., Jhaumeer Laulloo, S., Li Kam Wah, H. (eds) Chemistry for a Clean and Healthy Planet. ICPAC 2018. Springer, Cham. https://doi.org/10.1007/978-3-030-20283-5_4

Download citation

Publish with us

Policies and ethics

Search

Navigation