Abstract
Both recombinant and natural human IgG2 antibodies have several different disulfide bond isoforms, which possess different global structures, thermal stabilities, and biological activities. A detailed mapping of the structural difference among IgG2 disulfide isoforms, however, has not been established. In this work, we employed hydrogen/deuterium exchange mass spectrometry to study the conformation of three major IgG2 disulfide isoforms known as IgG2-B, IgG2-A1, and IgG2-A2 in two recombinant human IgG2 monoclonal antibodies. By comparing the protection factors between amino acid residues in isoforms B and A1 (the classical form), we successfully identified several local regions in which the IgG2-B isoform showed more solvent protection than the IgG2-A1 isoform. On the basis of three-dimensional structural models of IgG2, these identified regions were located on the Fab domains, close to the hinge, centered on the side where the two Fab arms faced each other in spatial proximity. We speculated that in the more solvent-protected B isoform, the two Fab arms were brought into contact by the nonclassical disulfide bonds, resulting in a more compact global structure. Loss of Fab domain flexibility in IgG2-B could limit its ability t...Continue Reading
References
Jan 1, 1971·The Biochemical Journal·C Milstein, B Frangione
Apr 1, 1993·Protein Science : a Publication of the Protein Society·Z Zhang, D L Smith
Aug 11, 2001·Science·E O SaphireI A Wilson
Oct 7, 2005·Mass Spectrometry Reviews·Thomas E Wales, John R Engen
Mar 15, 2008·The Journal of Biological Chemistry·Jette WypychAlain Balland
Mar 15, 2008·The Journal of Biological Chemistry·Thomas M DillonPavel V Bondarenko
Aug 21, 2008·The Journal of Biological Chemistry·Y Diana LiuGregory C Flynn
Mar 4, 2009·Biochemistry·Martin J AllenAlain Balland
Sep 22, 2009·Analytical Chemistry·Zhongqi Zhang
Dec 31, 2009·Analytical Chemistry·Bing ZhangSteven L Cockrill
Feb 2, 2010·Protein Science : a Publication of the Protein Society·Sandra LightleTheodore Oliphant
Aug 14, 2010·Analytical Chemistry·Dhanashri BagalPaul D Schnier
Jun 15, 2011·Pharmaceutical Research·Xiaoling WangSatish K Singh
May 11, 2012·Analytical Chemistry·Zhongqi ZhangGang Xiao
Jan 8, 2013·Molecular Immunology·Yaoqing Diana LiuGregory C Flynn
Sep 30, 2014·Protein Science : a Publication of the Protein Society·Yaoqing Diana LiuGregory C Flynn
Citations
Jan 27, 2016·Biochemistry·Jing FangZhongqi Zhang
Dec 31, 2015·Expert Review of Proteomics·Danilo DonnarummaNathalie Norais
Dec 3, 2015·Analytical Chemistry·Szabolcs FeketeKoen Sandra
Aug 11, 2015·Journal of Chromatography. a·Xiang CaoMary J Wirth
Sep 25, 2016·Analytica Chimica Acta·Bin DengDerek J Wilson
Feb 14, 2018·MAbs·Lily Liu-ShinGayathri Ratnaswamy
Oct 3, 2018·MAbs·Anja ResemannDetlev Suckau
Nov 28, 2018·Journal of Cellular Physiology·Meghdad Abdollahpour-AlitappehNader Bagheri
Oct 20, 2018·MAbs·Lily Pei-Yao Liu-ShinGayathri Ratnaswamy
May 16, 2019·The Journal of Biological Chemistry·Gar Kay HuiStephen J Perkins
Sep 11, 2019·Journal of Hematology & Oncology·Bo Yu, Delong Liu
Mar 18, 2017·Nature Reviews. Drug Discovery·Alain BeckNathalie Corvaïa
Jul 25, 2018·Scientific Reports·Sally Yu ShiYang Li
Sep 2, 2020·The Biochemical Journal·Michael J KnightChristopher R Pudney
Sep 22, 2017·MAbs·Guillaume TerralSarah Cianferani
Aug 21, 2016·Analytical Methods : Advancing Methods and Applications·Jude C LakbubHeather Desaire
Feb 4, 2021·Journal of the American Society for Mass Spectrometry·Dhanashri Bagal, Bradford W Gibson
Jan 30, 2021·Journal of Hematology & Oncology·Carmen CriscitielloGiuseppe Curigliano
Mar 1, 2019·Journal of the American Society for Mass Spectrometry·Sugyan M Dixit, Brandon T Ruotolo
Jun 2, 2021·Protein Science : a Publication of the Protein Society·Yoshitomo HamuroJennifer F Nemeth
Jun 25, 2021·Cancer Medicine·Wen-Qian LiJiu-Wei Cui
Apr 21, 2020·Analytical Chemistry·Zhongqi Zhang
May 27, 2020·Analytical Chemistry·Thomas BotzanowskiSarah Cianférani
Jun 30, 2018·Analytical Chemistry·Oscar Hernandez-AlbaSarah Cianférani
Apr 21, 2020·Journal of the American Society for Mass Spectrometry·Patanachai K LimpikiratiRichard W Vachet
Aug 28, 2021·Antibodies·Andrew T LucasWilliam C Zamboni
Jan 4, 2022·MAbs·Daniel W WoodallPavel V Bondarenko