Analysis and optimization of saturation transfer difference NMR experiments designed to map early self-association events in amyloidogenic peptides

The Journal of Physical Chemistry. B
Hao HuangGiuseppe Melacini

Abstract

Saturation transfer difference (STD) methods recently have been proposed to be a promising tool for self-recognition mapping at residue and atomic resolution in amyloidogenic peptides. Despite the significant potential of the STD approach for systems undergoing oligomer/monomer (O/M) equilibria, a systematic analysis of the possible artifacts arising in this novel application of STD experiments is still lacking. Here, we have analyzed the STD method as applied to O/M peptides, and we have identified three major sources of possible biases: offset effects, intramonomer cross-relaxation, and partial spin-diffusion within the oligomers. For the purpose of quantitatively assessing these artifacts, we employed a comparative approach that relies on 1-D and 2-D STD data acquired at different saturation frequencies on samples with different peptide concentrations and filtration states. This artifact evaluation protocol was applied to the Abeta(12-28) model system, and all three types of artifacts appear to affect the measured STD spectra. In addition, we propose a method to minimize the biases introduced by these artifacts in the Halpha STD distributions used to obtain peptide self-recognition maps at residue resolution. This method rel...Continue Reading

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Citations

Sep 29, 2011·European Biophysics Journal : EBJ·Jesus Angulo, Pedro M Nieto
Mar 7, 2012·The Journal of Biological Chemistry·Kenjiro OnoMasahito Yamada
Jun 9, 2009·Biophysical Chemistry·Yanfang LiangDerek J Wilson
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Jul 23, 2013·Biophysical Journal·Annie V RaditsisGiuseppe Melacini
Jun 12, 2010·Journal of Structural Biology·Shih-Chi LuoChinpan Chen
Dec 31, 2010·Biophysical Journal·Julijana Milojevic, Giuseppe Melacini
Jul 13, 2016·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Megumi InoueHeii Arai
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Feb 18, 2020·Frontiers in Neuroscience·Wing K ManGiuliana Fusco
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Aug 26, 2017·Journal of the American Chemical Society·Rashik AhmedGiuseppe Melacini
Jul 21, 2020·ACS Chemical Neuroscience·Sara García-ViñualesDanilo Milardi

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