Using mass spectrometry to study copper-protein binding under native and non-native conditions: beta-2-microglobulin

Analytical Chemistry
Jihyeon Lim, Richard W Vachet

Abstract

A method based on metal-catalyzed oxidation (MCO) reactions and mass spectrometry (MS) has been used to determine the Cu(II) binding sites in both native and unfolded conformations of beta-2-microglobulin (beta2m). Recent studies have shown that beta2m is destabilized and can form amyloid fibers in the presence of Cu(II). An increased affinity for Cu in unfolded states compared to that of the native state is suspected to facilitate overall protein destabilization. Cu-binding site information for native beta2m is difficult to obtain using traditional techniques because of its propensity to form amyloid fibers at relatively high protein concentrations in the presence of Cu and because of the nonspecific paramagnetic peak broadening observed in NMR analyses. In addition, Cu-binding information of unfolded beta2m is complicated by the high concentrations of denaturants (e.g., 8 M urea) needed to ensure protein unfolding. The MCO/MS approach has been successfully employed in this work to overcome these difficulties. The sensitivity of MS allowed the Cu-binding site of the native protein to be determined at the low concentrations of beta2m necessary to avoid amyloid fiber formation. Results indicate that the N-terminus of the protein...Continue Reading

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Citations

Jun 6, 2006·Journal of the American Society for Mass Spectrometry·Ani TempleScott Gronert
Jul 29, 2006·Journal of the American Society for Mass Spectrometry·Juma D BridgewaterRichard W Vachet
Dec 13, 2006·Journal of the American Society for Mass Spectrometry·Juma D BridgewaterRichard W Vachet
Jun 23, 2007·Journal of the American Society for Mass Spectrometry·R SrikanthRichard W Vachet
Sep 17, 2009·Biochemistry·Rapole SrikanthRichard W Vachet
Jan 28, 2009·Nature Structural & Molecular Biology·Matthew F CalabreseAndrew D Miranker
May 13, 2006·Annual Review of Biophysics and Biomolecular Structure·Keiji Takamoto, Mark R Chance
Aug 2, 2011·Chemical & Pharmaceutical Bulletin·Aya KojimaToshifumi Akizawa
Jan 23, 2009·Journal of Mass Spectrometry : JMS·Rapole SrikanthRichard W Vachet
Apr 21, 2009·Prion·Matthew F Calabrese, Andrew D Miranker
Aug 23, 2005·Biochimica Et Biophysica Acta·Niels H H Heegaard, Ersilia De Lorenzi
Aug 7, 2009·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Niels H H Heegaard
Mar 11, 2015·The Analyst·Ashley S PhillipsPerdita E Barran
Feb 29, 2008·Protein Science : a Publication of the Protein Society·Kwasi AntwiRichard W Vachet
May 5, 2017·The Journal of Biological Chemistry·Tyler M MarcinkoRichard W Vachet
Jun 6, 2020·Journal of the American Society for Mass Spectrometry·Tianying LiuRichard W Vachet
Oct 20, 2017·Journal of the American Chemical Society·Victor YinLars Konermann
Mar 12, 2020·Analytical Chemistry·Blaise G ArdenRichard W Vachet
Nov 7, 2012·Analytical Chemistry·Masafumi Fukuda, Toshifumi Takao
Nov 3, 2009·Bioorganic & Medicinal Chemistry·Atsushi MiyazakiAkira Takai

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