TY  - JOUR
AU  - Micsonai, András
AU  - Wien, F
AU  - Kernya, Linda
AU  - Lee, YH
AU  - Goto, Y
AU  - Refregiers, M
AU  - Kardos, József
TI  - Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy.
JF  - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
J2  - P NATL ACAD SCI USA
VL  - 112
PY  - 2015
IS  - 24
SP  - E3095
EP  - E3103
SN  - 0027-8424
DO  - 10.1073/pnas.1500851112
UR  - https://m2.mtmt.hu/api/publication/2902232
ID  - 2902232
N1  - Funding Agency and Grant Number: Bolyai Janos Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences; Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [K81950];  [KTIA_NAP_13-2-2014-0017]
            Funding text: We thank Ronald Wetzel for the polyQ CD spectrum and helpful advice. We thank Beata Vertessy, Judit Ovadi, Peter Tompa, Agnes Tantos, Jozsef Dobo, Balazs Major, Peter Gal, Maria Vass, Karoly Liliom, Peter Zavodszky, Mihaly Kovacs, Gabor Pal, and Laszlo Nyitray for providing protein samples for SRCD measurements, and Janos Kovacs for electron microscopy. J.K. was supported by Bolyai Janos Scholarship of the Hungarian Academy of Sciences. This work was supported by the Hungarian Scientific Research Fund (K81950) and KTIA_NAP_13-2-2014-0017. SRCD measurements were supported by SOLEIL (Proposals 20140646, 20130475, 20120589, 201110054, and 20110405).
AB  - 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 alpha/beta-mixed or beta-structure-rich proteins. The problem arises from the spectral diversity of beta-structures, which has hitherto been considered as an intrinsic limitation of the technique. The predictions are less reliable for proteins of unusual beta-structures such as membrane proteins, protein aggregates, and amyloid fibrils. Here, we show that the parallel/antiparallel orientation and the twisting of the beta-sheets account for the observed spectral diversity. We have developed a method called beta-structure selection (BeStSel) for the secondary structure estimation that takes into account the twist of beta-structures. This method can reliably distinguish parallel and antiparallel beta-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.
LA  - English
DB  - MTMT
ER  -