Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy

András Micsonai (1) , Frank Wien (2) , Linda Kernya (3) , Young-Ho Lee (3) , Yuji Goto (3) , Matthieu M. Refregiers (2) , József Kardos (1)

1 Institute of Biology [Budapest]
2 SSOLEIL - Synchrotron SOLEIL
3 Institute for Protein Research

Circular dichroism (CD) spectroscopy is a widely used technique for the study of protein structure. Numerous algorithms have been developed for the estimation of the secondary structure composi- tion from the CD spectra. These methods often fail to provide acceptable results on α/β-mixed or β-structure–rich proteins. The problem arises from the spectral diversity of β-structures, which has hitherto been considered as an intrinsic limitation of the tech- nique. The predictions are less reliable for proteins of unusual β-structures such as membrane proteins, protein aggregates, and amyloid fibrils. Here, we show that the parallel/antiparallel orien- tation and the twisting of the β-sheets account for the observed spectral diversity. We have developed a method called β-structure selection (BeStSel) for the secondary structure estimation that takes into account the twist of β-structures. This method can re- liably distinguish parallel and antiparallel β-sheets and accurately estimates the secondary structure for a broad range of proteins. Moreover, the secondary structure components applied by the method are characteristic to the protein fold, and thus the fold can be predicted to the level of topology in the CATH classification from a single CD spectrum. By constructing a web server, we offer a general tool for a quick and reliable structure analysis using con- ventional CD or synchrotron radiation CD (SRCD) spectroscopy for the protein science research community. The method is especially useful when X-ray or NMR techniques fail. Using BeStSel on data collected by SRCD spectroscopy, we investigated the structure of amyloid fibrils of various disease-related proteins and peptides.

Mots clés: circular dichroism; secondary structure determination; protein fold; protein aggregation; amyloid

Domaines: Biophysique [physics.bio-ph]

András Micsonai, Frank Wien, Linda Kernya, Young-Ho Lee, Yuji Goto, et al.. Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112, pp.E3095-E3103. ⟨10.1073/pnas.1500851112⟩. ⟨hal-01485547⟩