Self-assembly of designed coiled coil peptides studied by small-angle X-ray scattering and analytical ultracentrifugation

Malik, Leila; Nygaard, Jesper; Christensen, Niels J.; Streicher, Werner W.; Thulstrup, Peter W.; Arleth, Lise; Jensen, Knud J.
Journal of Peptide Science, 2013

α-Helical coiled coil structures, which are noncovalently associated heptad repeat peptide sequences, are ubiquitous in nature. Similar amphipathic repeat sequences have also been found in helix-containing proteins and have played a central role in de novo design of proteins. In addition, they are promising tools for the construction of nanomaterials. Small-angle X-ray scattering (SAXS) has emerged as a new biophysical technique for elucidation of protein topology. Here, we describe a systematic study of the self-assembly of a small ensemble of coiled coil sequences using SAXS and analytical ultracentrifugation (AUC), which was correlated with molecular dynamics simulations. Our results show that even minor sequence changes have an effect on the folding topology and the self-assembly and that these differences can be observed by a combination of AUC, SAXS, and circular dichroism spectroscopy. A small difference in these methods was observed, as SAXS for one peptide and revealed the presence of a population of longer aggregates, which was not observed by AUC.

KEYWORDS: Bio-SAXS, Self-assembly