The conformation of the Congo-red ligand bound to amyloid fibrils HET-s(218–289): a solid-state NMR study

Abstract

We have previously shown that Congo red (CR) binds site specifically to amyloid fibrils formed by HET-s(218–289) with the long axis of the CR molecule almost parallel to the fibril axis. HADDOCK docking studies indicated that CR adopts a roughly planar conformation with the torsion angle ϕ characterizing the relative orientation of the two phenyl rings being a few degrees. In this study, we experimentally determine the torsion angle ϕ at the center of the CR molecule when bound to HET-s(218–289) amyloid fibrils using solid-state NMR tensor-correlation experiments. The method described here relies on the site-specific 13C labeling of CR and on the analysis of the two-dimensional magic-angle spinning tensor-correlation spectrum of 13C2-CR. We determined the torsion angle ϕ to be 19°.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Ashburn TT, Han H, McGuinness BF, Lansbury PT (1996) Amyloid probes based on Congo red distinguish between fibrils comprising different peptides. Chem Biol 3:351–358

    Article  Google Scholar 

  2. Bak M, Rasmussen JT, Nielsen NC (2000) SIMPSON: a general simulation program for solid-state NMR spectroscopy. J Magn Reson 147:296–330

    ADS  Article  Google Scholar 

  3. Bely M, Makovitzky J (2006) Sensitivity and specificity of Congo red staining according to Romhanyi. Comparison with Puchtler‘s or Bennhold’s methods. Acta Histochem 108:175–180

    Article  Google Scholar 

  4. Benditt EP, Eriksen N, Berglund C (1970) Congo red dichroism with dispersed amyloid fibrils, an extrinsic cotton effect. Proc Natl Acad Sci USA 66:1044–1051

    ADS  Article  Google Scholar 

  5. Böttiger P (1884) Synthesis of Congo red, Deutsches Reichs Patent 28753

  6. Eaton VJ, Steele D (1973) Dihedral Angle of biphenyl in solution and molecular force-field. J Chem Soc Faraday Trans 2 69:1601–1608

    Article  Google Scholar 

  7. Eichele K (2015) HBA: Herzfeld-Berger analysis program. http://anorganik.uni-tuebingen.de/klaus/soft/indexphp?p=hba/hba Version1.7.5

  8. Facelli JC, Grant DM, Michl J (1987) C-13 shielding tensors: experimental and theoretical determination. Acc Chem Res 20:152–158

    Article  Google Scholar 

  9. Frid P, Anisimov SV, Popovic N (2007) Congo red and protein aggregation in neurodegenerative diseases. Brain Res Rev 53:135–160

    Article  Google Scholar 

  10. Glenner GG (1980) Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts). N Engl J Med 302:1283–1292

    Article  Google Scholar 

  11. Hagemeyer A, Schmidt-Rohr K, Spiess HW (1989) Two-dimensional nuclear magnetic resonance experiments for studying molecular order and dynamics in static and in rotating solids. Adv Magn Opt Reson 13:85–130

    Article  Google Scholar 

  12. Herrmann US et al (2015) Structure-based drug design identifies polythiophenes as antiprion compounds. Sci Transl Med 7:299ra123

    Article  Google Scholar 

  13. Herzfeld J, Berger AE (1980) Sideband intensities in NMR-spectra of samples spinning at the magic angle. J Chem Phys 73:6021–6030

    ADS  Article  Google Scholar 

  14. Kentgens A, De Boer E, Veeman WS (1987) Ultraslow molecular motions in crystalline polyoxymethylene: a complete elucidation using two-dimensional solid-state NMR. J Chem Phys 87:6859–6866

    ADS  Article  Google Scholar 

  15. Khurana R, Uversky VN, Nielsen L, Fink AL (2001) Is Congo red an amyloid-specific dye? J Biol Chem 276:22715–22721

    Article  Google Scholar 

  16. Miura T, Yamamiya C, Sasaki M, Suzuki K, Takeuchi H (2002) Binding mode of Congo red to Alzheimer’s amyloid beta-peptide studied by UV Raman spectroscopy. J Raman Spectrosc 33:530–535

    ADS  Article  Google Scholar 

  17. Ojala WH, Ojala CR, Gleason WB (1995) The X-ray crystal-structure of the sulfonated azo-dye Congo-red, a nonpeptidic inhibitor of Hiv-1 protease which also binds to reverse-transcriptase and amyloid proteins. Antiviral Chem Chemother 6:25–33

    Article  Google Scholar 

  18. Puchtler H, Sweat F, Levine M (1962) On binding of Congo red by amyloid. J Histochem Cytochem 10:355–364

    Article  Google Scholar 

  19. Raleigh DP, Levitt MH, Griffin RG (1988) Rotational resonance in solid-state NMR. Chem Phys Lett 146:71–76

    ADS  Article  Google Scholar 

  20. Schütz AK et al (2011) The amyloid-Congo red interface at atomic resolution. Angew Chem Int Ed Engl 50:5956–5960

    Article  Google Scholar 

  21. Smith SA, Levante TO, Meier BH, Ernst RR (1994) Computer-simulations in magnetic-resonance: an object-oriented programming approach. J Magn Reson Ser A 106:75–105

    ADS  Article  Google Scholar 

  22. Smith AA et al (2017) Partially-deuterated samples of HET-s(218–289) fibrils: assignment and deuterium isotope effect. J Biomol NMR 67:109–119

    Article  Google Scholar 

  23. Suzuki H (1959) Relations between electronic absorption spectra and spatial configurations of conjugated systems.1. Biphenyl. Bull Chem Soc Jpn 32:1340–1350

    Article  Google Scholar 

  24. Tycko R, Berger AE (1999) Dual processing of two-dimensional exchange data in magic angle spinning NMR of solids. J Magn Reson 141:141–147

    ADS  Article  Google Scholar 

  25. Tycko R, Weliky DP, Berger AE (1996) Investigation of molecular structure in solids by two-dimensional NMR exchange spectroscopy with magic angle spinning. J Chem Phys 105:7915–7930

    ADS  Article  Google Scholar 

  26. van Beek JD (2007) matNMR: a flexible toolbox for processing, analyzing and visualizing magnetic resonance data in Matlab. J Magn Reson Ser A 187:19–26

    ADS  Article  Google Scholar 

  27. Van Dongen Torman J, Veeman WS (1978) C-13 chemical shielding tensors in para-xylene. J Chem Phys 68:3233–3235

    ADS  Article  Google Scholar 

  28. Weliky DP, Tycko R (1996) Determination of peptide conformations by two-dimensional magic angle spinning NMR exchange spectroscopy with rotor synchronization. J Am Chem Soc 118:8487–8488

    Article  Google Scholar 

  29. Westermark GT, Johnson KH, Westermark P (1999) Staining methods for identification of amyloid in tissue. Method Enzymol 309:3–25

    Article  Google Scholar 

  30. Westermark P et al (2007) A primer of amyloid nomenclature. Amyloid 14:179–183

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank Albert A. Smith for helpful discussions. This work has been supported by the Swiss National Science Foundation SNF (Grant 200020_159707 and 200020_146757) and by the French ANR (ANR-14-CE09-0024B).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Matthias Ernst or Beat H. Meier.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 451 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gowda, C., Zandomeneghi, G., Zimmermann, H. et al. The conformation of the Congo-red ligand bound to amyloid fibrils HET-s(218–289): a solid-state NMR study. J Biomol NMR 69, 207–213 (2017). https://doi.org/10.1007/s10858-017-0148-z

Download citation

Keywords

  • MAS
  • Amyloid fibrils
  • Congo red
  • Rotor-synchronized tensor-correlation experiments