Skip to main content
SpringerLink
Log in
Book cover

Membrane Proteins pp 183–196Cite as

Prediction and Design of Outer Membrane Protein–Protein Interactions

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1063))

Abstract

Protein–protein interactions (PPI) play central roles in biological processes, motivating us to understand the structural basis underlying affinity and specificity. In this chapter, we focus on biochemical and computational design strategies of assessing and detecting PPIs of β-barrel outer membrane proteins (OMPs). A few case studies are presented highlighting biochemical techniques used to dissect the energetics of oligomerization and determine amino acids forming the key interactions of the PPI sites. Current computational strategies for detecting/predicting PPIs are introduced, and examples of computational and rational engineering strategies applied to OMPs are presented.

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

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
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

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

Abbreviations

OMP:

Outer membrane protein

OmpLA:

Outer membrane phospholipase A

PPI:

Protein–protein interaction

VDAC:

Voltage-dependent anion channel

References

  1. De Las Rivas J, Fontanillo C (2010) Protein-protein interactions essentials: key concepts to building and analyzing interactome networks. PLoS Comput Biol 6(6):e1000807

    Article  PubMed  Google Scholar 

  2. Cusick ME et al (2005) Interactome: gateway into systems biology. Hum Mol Genet 14(Spec No. 2):R171–R181

    Article  PubMed  CAS  Google Scholar 

  3. Schleiff E et al (2003) Characterization of the translocon of the outer envelope of chloroplasts. J Cell Biol 160(4):541–551

    Article  PubMed  CAS  Google Scholar 

  4. Schein SJ, Colombini M, Finkelstein A (1976) Reconstitution in planar lipid bilayers of a voltage-dependent anion-selective channel obtained from paramecium mitochondria. J Membr Biol 30(2):99–120

    PubMed  CAS  Google Scholar 

  5. Dong C et al (2006) Wza the translocon for E. coli capsular polysaccharides defines a new class of membrane protein. Nature 444(7116):226–229

    Article  PubMed  CAS  Google Scholar 

  6. Jones S, Thornton JM (1997) Prediction of protein-protein interaction sites using patch analysis. J Mol Biol 272(1):133–143

    Article  PubMed  CAS  Google Scholar 

  7. Zhou FX et al (2000) Interhelical hydrogen bonding drives strong interactions in membrane proteins. Nat Struct Biol 7(2):154–160

    Article  PubMed  CAS  Google Scholar 

  8. Choma C et al (2000) Asparagine-mediated self-association of a model transmembrane helix. Nat Struct Biol 7(2):161–166

    Article  PubMed  CAS  Google Scholar 

  9. Senes A, Engel DE, DeGrado WF (2004) Folding of helical membrane proteins: the role of polar, GxxxG-like and proline motifs. Curr Opin Struct Biol 14(4):465–479

    Article  PubMed  CAS  Google Scholar 

  10. Senes A, Ubarretxena-Belandia I, Engelman DM (2001) The Calpha –-H…O hydrogen bond: a determinant of stability and specificity in transmembrane helix interactions. Proc Natl Acad Sci USA 98(16):9056–9061

    Article  PubMed  CAS  Google Scholar 

  11. Senes A, Gerstein M, Engelman DM (2000) Statistical analysis of amino acid patterns in transmembrane helices: the GxxxG motif occurs frequently and in association with beta-branched residues at neighboring positions. J Mol Biol 296(3):921–936

    Article  PubMed  CAS  Google Scholar 

  12. Schulz GE (2002) The structure of bacterial outer membrane proteins. Biochim Biophys Acta 1565(2):308–317

    Article  PubMed  CAS  Google Scholar 

  13. Popot JL, Engelman DM (1990) Membrane protein folding and oligomerization: the two-stage model. Biochemistry 29(17):4031–4037

    Article  PubMed  CAS  Google Scholar 

  14. Lemmon MA et al (1992) Sequence specificity in the dimerization of transmembrane alpha-helices. Biochemistry 31(51):12719–12725

    Article  PubMed  CAS  Google Scholar 

  15. Lemmon MA et al (1992) Glycophorin A dimerization is driven by specific interactions between transmembrane alpha-helices. J Biol Chem 267(11):7683–7689

    PubMed  CAS  Google Scholar 

  16. Dekker N et al (1997) Dimerization regulates the enzymatic activity of Escherichia coli outer membrane phospholipase A. J Biol Chem 272(6):3179–3184

    Article  PubMed  CAS  Google Scholar 

  17. Stanley AM et al (2006) Energetics of outer membrane phospholipase A (OMPLA) dimerization. J Mol Biol 358(1):120–131

    Article  PubMed  CAS  Google Scholar 

  18. Doura AK et al (2004) Sequence context modulates the stability of a GxxxG-mediated transmembrane helix-helix dimer. J Mol Biol 341(4):991–998

    Article  PubMed  CAS  Google Scholar 

  19. Faham S et al (2004) Side-chain contributions to membrane protein structure and stability. J Mol Biol 335(1):297–305

    Article  PubMed  CAS  Google Scholar 

  20. Ebie Tan A, Fleming KG (2008) Outer membrane phospholipase a dimer stability does not correlate to occluded surface area. Biochemistry 47(46):12095–12103

    Article  PubMed  Google Scholar 

  21. Cristian L et al (2005) Synergistic interactions between aqueous and membrane domains of a designed protein determine its fold and stability. J Mol Biol 348(5):1225–1233

    Article  PubMed  CAS  Google Scholar 

  22. Stanley AM, Fleming KG (2007) The role of a hydrogen bonding network in the transmembrane beta-barrel OMPLA. J Mol Biol 370(5): 912–924

    Article  PubMed  CAS  Google Scholar 

  23. Burgess NK et al (2008) Beta-barrel proteins that reside in the Escherichia coli outer membrane in vivo demonstrate varied folding behavior in vitro. J Biol Chem 283(39):26748–26758

    Article  PubMed  CAS  Google Scholar 

  24. Hoogenboom BW et al (2007) The supramolecular assemblies of voltage-dependent anion channels in the native membrane. J Mol Biol 370(2):246–255

    Article  PubMed  CAS  Google Scholar 

  25. Granville DJ, Gottlieb RA (2003) The mitochondrial voltage-dependent anion channel (VDAC) as a therapeutic target for initiating cell death. Curr Med Chem 10(16): 1527–1533

    Article  PubMed  CAS  Google Scholar 

  26. Shoshan-Barmatz V, Gincel D (2003) The voltage-dependent anion channel: characterization, modulation, and role in mitochondrial function in cell life and death. Cell Biochem Biophys 39(3):279–292

    Article  PubMed  CAS  Google Scholar 

  27. Zalk R et al (2005) Oligomeric states of the voltage-dependent anion channel and cytochrome c release from mitochondria. Biochem J 386(Pt 1):73–83

    PubMed  CAS  Google Scholar 

  28. Hiller S et al (2008) Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science 321(5893):1206–1210

    Article  PubMed  CAS  Google Scholar 

  29. Geula S et al (2012) Structure-based analysis of VDAC1 protein: defining oligomer contact sites. J Biol Chem 287(3):2179–2190

    Article  PubMed  CAS  Google Scholar 

  30. Protein Data Bank. http://www.rcsb.org/pdb.

  31. Fairman JW, Noinaj N, Buchanan SK (2011) The structural biology of beta-barrel membrane proteins: a summary of recent reports. Curr Opin Struct Biol 21(4):523–531

    Article  PubMed  CAS  Google Scholar 

  32. Hsieh D, Davis A, Nanda V (2012) A knowledge-based potential highlights unique features of membrane alpha-helical and beta-barrel protein insertion and folding. Protein Sci 21(1):50–62

    Article  PubMed  CAS  Google Scholar 

  33. Senes A et al (2007) E(z), a depth-dependent potential for assessing the energies of insertion of amino acid side-chains into membranes: derivation and applications to determining the orientation of transmembrane and interfacial helices. J Mol Biol 366(2):436–448

    Article  PubMed  CAS  Google Scholar 

  34. Schramm CA et al (2012) Knowledge-based potential for positioning membrane-associated structures and assessing residue-specific energetic contributions. Structure 20(5):924–935

    Article  PubMed  CAS  Google Scholar 

  35. Adamian L, Naveed H, Liang J (2011) Lipid-binding surfaces of membrane proteins: evidence from evolutionary and structural analysis. Biochim Biophys Acta 1808(4): 1092–1102

    Article  PubMed  CAS  Google Scholar 

  36. Jackups R Jr, Liang J (2005) Interstrand pairing patterns in beta-barrel membrane proteins: the positive-outside rule, aromatic rescue, and strand registration prediction. J Mol Biol 354(4):979–993

    Article  PubMed  CAS  Google Scholar 

  37. Naveed H et al (2012) Predicting three-dimensional structures of transmembrane domains of beta-barrel membrane proteins. J Am Chem Soc 134(3):1775–1781

    Article  PubMed  CAS  Google Scholar 

  38. Naveed H, Jackups R Jr, Liang J (2009) Predicting weakly stable regions, oligomerization state, and protein-protein interfaces in transmembrane domains of outer membrane proteins. Proc Natl Acad Sci USA 106(31):12735–12740

    Article  PubMed  CAS  Google Scholar 

  39. Merkel JS, Regan L (1998) Aromatic rescue of glycine in beta sheets. Fold Des 3(6): 449–455

    Article  PubMed  CAS  Google Scholar 

  40. Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6(3):197–208

    Article  PubMed  CAS  Google Scholar 

  41. AAINDEX. http://www.genome.jp/aaindex.

  42. Hayat S et al (2011) Prediction of the exposure status of transmembrane beta barrel residues from protein sequence. J Bioinforma Comput Biol 9(1):43–65

    Article  CAS  Google Scholar 

  43. Adamian L et al (2005) Empirical lipid propensities of amino acid residues in multispan alpha helical membrane proteins. Proteins 59(3):496–509

    Article  PubMed  CAS  Google Scholar 

  44. Jung Y, Bayley H, Movileanu L (2006) Temperature-responsive protein pores. J Am Chem Soc 128(47):15332–15340

    Article  PubMed  CAS  Google Scholar 

  45. Gu LQ et al (1999) Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adapter. Nature 398(6729):686–690

    Article  PubMed  CAS  Google Scholar 

  46. Korkmaz-Ozkan F et al (2010) Correlation between the OmpG secondary structure and its pH-dependent alterations monitored by FTIR. J Mol Biol 401(1):56–67

    Article  PubMed  Google Scholar 

  47. Tatko CD et al (2006) Polar networks control oligomeric assembly in membranes. J Am Chem Soc 128(13):4170–4171

    Article  PubMed  CAS  Google Scholar 

  48. Hall AR et al (2010) Hybrid pore formation by directed insertion of alpha-haemolysin into solid-state nanopores. Nat Nanotechnol 5(12):874–877

    Article  PubMed  CAS  Google Scholar 

  49. Mohammad MM, Howard KR, Movileanu L (2011) Redesign of a plugged beta-barrel membrane protein. J Biol Chem 286(10): 8000–8013

    Article  PubMed  CAS  Google Scholar 

  50. Muhammad N et al (2011) Engineering of the E. coli outer membrane protein FhuA to overcome the hydrophobic mismatch in thick polymeric membranes. J Nanobiotechnology 9:8

    Article  PubMed  CAS  Google Scholar 

  51. Georgiou G et al (1997) Display of heterologous proteins on the surface of microorganisms: from the screening of combinatorial libraries to live recombinant vaccines. Nat Biotechnol 15(1):29–34

    Article  PubMed  CAS  Google Scholar 

  52. Varadarajan N et al (2008) Highly active and selective endopeptidases with programmed substrate specificities. Nat Chem Biol 4(5):290–294

    Article  PubMed  CAS  Google Scholar 

  53. Slovic AM et al (2004) Computational design of water-soluble analogues of the potassium channel KcsA. Proc Natl Acad Sci USA 101(7):1828–1833

    Article  PubMed  CAS  Google Scholar 

  54. Kono H, Saven JG (2001) Statistical theory for protein combinatorial libraries. Packing interactions, backbone flexibility, and the sequence variability of a main-chain structure. J Mol Biol 306(3):607–628

    Article  PubMed  CAS  Google Scholar 

  55. Ma D et al (2008) NMR studies of a channel protein without membranes: structure and dynamics of water-solubilized KcsA. Proc Natl Acad Sci USA 105(43):16537–16542

    Article  PubMed  CAS  Google Scholar 

  56. Yin H et al (2007) Computational design of peptides that target transmembrane helices. Science 315(5820):1817–1822

    Article  PubMed  CAS  Google Scholar 

  57. Shandler SJ et al (2011) Computational design of a beta-peptide that targets transmembrane helices. J Am Chem Soc 133(32): 12378–12381

    Article  PubMed  CAS  Google Scholar 

  58. Korendovych IV et al (2010) De novo design and molecular assembly of a transmembrane diporphyrin-binding protein complex. J Am Chem Soc 132(44):15516–15518

    Article  PubMed  CAS  Google Scholar 

  59. Chen M et al (2008) Outer membrane protein G: engineering a quiet pore for biosensing. Proc Natl Acad Sci U S A 105(17):6272–6277

    Article  PubMed  CAS  Google Scholar 

  60. Naveed H et al (2012) Engineered oligomerization state of OmpF protein through computational design decouples oligomer dissociation from unfolding. J Mol Biol 419(1–2):89–101

    Article  PubMed  CAS  Google Scholar 

  61. Gessmann D et al (2011) Improving the resistance of a eukaryotic beta-barrel protein to thermal and chemical perturbations. J Mol Biol 413(1):150–161

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School—UMDNJ, Piscataway, NJ, USA

    Vikas Nanda

  2. Department of Biochemistry and Molecular Biology, Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School—UMDNJ, Piscataway, NJ, USA

    Daniel Hsieh & Alexander Davis

Authors
  1. Vikas Nanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Dept. of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, USA

    Giovanna Ghirlanda

  2. Department of Biochemistry, University of Wisconsin, Madison, Madison, Wisconsin, USA

    Alessandro Senes

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Nanda, V., Hsieh, D., Davis, A. (2013). Prediction and Design of Outer Membrane Protein–Protein Interactions. In: Ghirlanda, G., Senes, A. (eds) Membrane Proteins. Methods in Molecular Biology, vol 1063. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-583-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-583-5_10

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-582-8

  • Online ISBN: 978-1-62703-583-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation