Studying "invisible" excited protein states in slow exchange with a major state conformation

Journal of the American Chemical Society
Pramodh VallurupalliLewis E Kay

Abstract

Ever since its initial development, solution NMR spectroscopy has been used as a tool to study conformational exchange. Although many systems are amenable to relaxation dispersion approaches, cases involving highly skewed populations in slow chemical exchange have, in general, remained recalcitrant to study. Here an experiment to detect and characterize "invisible" excited protein states in slow exchange with a visible ground-state conformation (excited-state lifetimes ranging from ∼5 to 50 ms) is presented. This method, which is an adaptation of the chemical exchange saturation transfer (CEST) magnetic resonance imaging experiment, involves irradiating various regions of the spectrum with a weak B(1) field while monitoring the effect on the visible major-state peaks. The variation in major-state peak intensities as a function of frequency offset and B(1) field strength is quantified to obtain the minor-state population, its lifetime, and excited-state chemical shifts and line widths. The methodology was validated with (15)N CEST experiments recorded on an SH3 domain-ligand exchanging system and subsequently used to study the folding transition of the A39G FF domain, where the invisible unfolded state has a lifetime of ∼20 ms. ...Continue Reading

References

Dec 2, 1975·Biochemistry·R H AustinI C Gunsalus
Dec 13, 1991·Science·H FrauenfelderP G Wolynes
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Jan 15, 1999·Journal of Magnetic Resonance·M Rance Palmer AG3rd
Dec 22, 1999·Journal of Biomolecular NMR·J P LoriaA G Palmer
Jul 13, 2001·Journal of the American Chemical Society·A Mittermaier, L E Kay
Mar 25, 2004·Journal of the American Chemical Society·Dmitry M KorzhnevLewis E Kay
Apr 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Per JemthAlan R Fersht
May 4, 2004·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Jinyuan ZhouPeter C M Van Zijl
Aug 12, 2004·Chemical Reviews·Arthur G Palmer
Jan 18, 2006·Nature Chemical Biology·Brian P EnglishX Sunney Xie
Feb 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·D Flemming Hansen, Jens J Led
Apr 15, 2006·Science·Anthony Mittermaier, Lewis E Kay
Nov 16, 2007·The Journal of Physical Chemistry. B·D Flemming HansenLewis E Kay
Nov 17, 2007·Proceedings of the National Academy of Sciences of the United States of America·Pramodh VallurupalliLewis E Kay
Feb 2, 2008·Journal of the American Chemical Society·D Flemming HansenLewis E Kay
Aug 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Pramodh VallurupalliLewis E Kay
Jan 20, 2009·Journal of the American Chemical Society·Patrik LundströmLewis E Kay
Mar 18, 2009·Biophysical Journal·Philipp NeudeckerLewis E Kay
Oct 21, 2009·Nature Chemical Biology·David D BoehrPeter E Wright
Dec 7, 2010·Journal of the American Chemical Society·Kamil TamiolaFrans A A Mulder
Feb 22, 2011·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Peter C M van Zijl, Nirbhay N Yadav

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Citations

Feb 7, 2013·Journal of Biomolecular NMR·Alexandar L HansenLewis E Kay
Jul 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ashok Sekhar, Lewis E Kay
Apr 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Alexandar L Hansen, Lewis E Kay
Aug 29, 2014·Journal of the Royal Society, Interface·Tobias Sikosek, Hue Sun Chan
Jun 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Dong LongLewis E Kay
Apr 26, 2016·Progress in Nuclear Magnetic Resonance Spectroscopy·Paul Schanda, Matthias Ernst
Feb 24, 2016·Journal of Magnetic Resonance·Arthur G Palmer
Aug 5, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ashok SekharLewis E Kay
Mar 5, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jaka KrageljMalene Ringkjøbing Jensen
Apr 22, 2015·Biochimica Et Biophysica Acta·Zhu LiuChun Tang
Jan 7, 2016·Chemical Reviews·George P Lisi, J Patrick Loria
Aug 31, 2016·Progress in Nuclear Magnetic Resonance Spectroscopy·Ayako FurukawaKenji Sugase
Mar 15, 2015·Current Opinion in Structural Biology·Bo Zhao, Qi Zhang
Oct 2, 2015·Journal of the American Chemical Society·Elise DelaforgeMartin Blackledge
Apr 19, 2016·Quarterly Reviews of Biophysics·Michael KovermannMagnus Wolf-Watz
Sep 10, 2015·Journal of Biomolecular NMR·Marta G CarneiroDonghan Lee
Sep 25, 2012·Current Opinion in Structural Biology·Masanori OsawaIchio Shimada
Mar 25, 2014·Journal of Magnetic Resonance·Arthur G Palmer
Jul 15, 2015·Nature Structural & Molecular Biology·Sven BrüschweilerJames J Chou
Jun 24, 2015·ELife·Tao Xie, Charalampos G Kalodimos
Dec 18, 2013·Journal of Magnetic Resonance·Noritaka NishidaIchio Shimada
Feb 25, 2015·Quarterly Reviews of Biophysics·Nicholas J Anthis, G Marius Clore
Dec 4, 2014·Journal of Biomolecular NMR·Yang Zhou, Daiwen Yang
Apr 26, 2016·Chemical Reviews·Stephen Boulton, Giuseppe Melacini
May 4, 2016·Proceedings of the National Academy of Sciences of the United States of America·Ashok SekharLewis E Kay
Apr 26, 2016·The Journal of Physical Chemistry. B·Alex William JacobitzJeff Wereszczynski
Sep 27, 2016·Frontiers in Molecular Biosciences·Luca MollicaRobert Schneider
Oct 11, 2016·Frontiers in Physiology·Mayra de A Marques, Guilherme A P de Oliveira
Nov 12, 2013·Journal of Molecular Biology·Guillaume BouvigniesLewis E Kay
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Ashok SekharLewis E Kay

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