title: Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy.
abstract: 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 composition 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 technique. 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 orientation 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 reliably 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 conventional 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.
authors.affiliation: Department of Biochemistry and MTA-ELTE NAP B Neuroimmunology Research Group, Institute of Biology, Eötvös Loránd University, H-1117 Budapest, Hungary;
authors.forename: András
authors.initials: A
authors.lastname: Micsonai
authors.affiliation: DISCO Beamline, Synchrotron SOLEIL, 91192 Gif-sur-Yvette, France;
authors.forename: Frank
authors.initials: F
authors.lastname: Wien
authors.affiliation: Department of Biochemistry and MTA-ELTE NAP B Neuroimmunology Research Group, Institute of Biology, Eötvös Loránd University, H-1117 Budapest, Hungary;
authors.forename: Linda
authors.initials: L
authors.lastname: Kernya
authors.affiliation: Division of Protein Structural Biology, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Division of Protein Structural Biology, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
authors.affiliation: DISCO Beamline, Synchrotron SOLEIL, 91192 Gif-sur-Yvette, France;
authors.forename: Matthieu
authors.initials: M
authors.lastname: Réfrégiers
authors.affiliation: Department of Biochemistry and MTA-ELTE NAP B Neuroimmunology Research Group, Institute of Biology, Eötvös Loránd University, H-1117 Budapest, Hungary; kardos@elte.hu.
authors.forename: József
authors.initials: J
authors.lastname: Kardos
mesh_terms: D000465:Algorithms; D016229:Amyloid beta-Peptides / Q000737:chemistry; D055592:Biophysical Phenomena; D002942:Circular Dichroism / Q000379:methods* / Q000706:statistics & numerical data; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D066329:Protein Aggregates; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D001613:beta 2-Microglobulin / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; D066329:Protein Aggregates; D011506:Proteins; C075222:amyloid beta-protein (1-42); D001613:beta 2-Microglobulin; C097188:polyglutamine
keywords: amyloid; circular dichroism; protein aggregation; protein fold; secondary structure determination