EMBL Hamburg Biological
Small Angle Scattering

Structural investigation of protein and peptide fibrillation – published and emerging results

Bente Vestergaard

Department of Drug Design and Pharmacology, University of Copenhagen, Denmark

Protein fibrillation is associated with several severe diseases, notably also the large neurodegenerative diseases Alzheimer's and Parkinson's disease. Structural investigations of protein fibrillation are inherently challenging, due to the co-existence of several structural species at very different length- and time-scales. In the Copenhagen BioSAXS group we apply solution small angle X-ray scattering for such analysis, elucidating structural parameters of intermediately or transiently formed structural species (1,2,3) and the principles of fibril elongation (11). The structural hierarchy of fibrils is well investigated with hybrid methods (4) and some of our more recent results, combining primarily X-ray scattering, diffraction and electron microscopy enable quasi-atomic resolution modeling of peptide fibrils (5). Oligomeric precursors in some cases accumulate during fibrillation (1,2), but other systems fibrillate without significant accumulation of intermediate structures (5, 6, 8). The macroscopic morphology of fibrils exhibits extensive variation (1-9), which may correlate with early structural changes (7, 8). Importantly, intermediate structural species associate with membrane perturbing and potential cytotoxic effects (11). All the above topics will – if time permits – be touched during the presentation.


  1. A helical structural nucleus is the primary elongating unit of insulin amyloid fibrils. Vestergaard, B., Groenning, M., Roessle, M., Kastrup, J.S., van de Weert, M., Flink, J.M., Frokjaer, S., Gajhede, M., Svergun, D.I. (2007) PLoS Biology, 5(5):e134
  2. Low resolution structure of a vesicle disrupting α-synuclein oligomer that accumulates during fibrillation. Giehm, L.; Svergun, D.I.; Otzen, D.E. and Vestergaard, B. (2011) Proc. Natl. Acad. Sci. USA. 108(8):3246-51
  3. Structural Characterisation of Pre-fibrillar intermediates and amyloid fibrils by small angle X-ray scattering. Langkilde, A.E. and Vestergaard, B. (2012). Methods in Molecular Biology, 849, 137-55
  4. Atomic structure and hierarchical assembly of a cross-b amyloid fibril. Fitzpatrick, AWP; Debelouchina, GT; Bayro, MJ; Clare, DK; Caporini, MA; Vikram, SB; Jaroniec, CP; Wang, L; Ladizhansky, V; Müller, SA; MacPhee, CE; Waudby, CA; Mott, HR; De Simone, A; Knowles, TPJ; Saibil, SR; Vendruscolo, M; Orlova EV; Griffin, RG & Dobson CM (2013) Proc. Natl. Acad. Sci. USA 110(14): 5468-5473
  5. The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy. Langkilde, AE; Morris, K; Serpell, LC; Svergun, DI & Vestergaard, B; manuscript in review
  6. Evidence for a Dynamic Protofibril Structure: A Considerably Unfolded Transthyretin Monomer Preceeds and Exchanges with Amyloid Protofibrils. Groenning, M; Campos, RI; Hirschberg, D; Hammarström, P & Vestergaard, B; manuscript in preparation
  7. Unlocked Concanavalin A Forms Amyloid-like Fibrils from Coagulation of long-lived 'Crinkled' Intermediates. Vetri, V., Leone, M., Morozova-Roche, L., Vestergaard, B. & Foderà, V. (2013). PLoS One, 8(7):e68912
  8. Observation of the Early Structural Changes Leading to the Formation of Protein Superstructures. Foderà, V; Vetri, V; Wind, TS; Noppe,, W., Cornett, C., Donald, A.M.; Morozova-Roche, L; & Vestergaard, B (2014) Journal of Physical Chemistry Letters, 5, 3254-3258.
  9. Wildtype and A30P mutant alphasynuclein form different fibril structures. Nielsen, S.B.; Macchi, F., Raccosta, S., Langkilde, A.E., Giehm, L. Kyrsting, A., Svane, A.S.P., Manno, M., Christiansen, G., Nielsen, N.C., Oddershede, L., Vestergaard, B. & Otzen, D.E. (2013) PLoS One, 8(7):e67713
  10. Protein:lipid co-aggregates are formed during α-synuclein-induced disruption of lipid bilayers. van Maarschalkerweerd, A., Vetri, V., Langkilde, A.E., Foderà, V. and Vestergaard, B. (2014) Biomacromolecules. Accepted
  11. Direct observation of the Elongation Principle for α-Synuclein Amyloid Fibrils. Pedersen, M.N. Foderà, V., Horvath, I., van Maarschalkerweerd, A., Toft, K.N., Weise, C., Almqvist, F., Wolf-Watz, M., Wittung-Staffshede, P. and Vestergaard, B. Submitted

Date/time: Friday, 31 October 2014, 16:00

  Last modified: October 16, 2014

© BioSAXS group 2014