The structure of the IgE Cepsilon2 domain and its role in stabilizing the complex with its high-affinity receptor FcepsilonRIalpha

Nature Structural Biology
J M McDonnellD Cowburn

Abstract

The stability of the complex between IgE and its high-affinity receptor, FcepsilonRI, on mast cells is a critical factor in the allergic response. The long half-life of the complex of IgE bound to this receptor in situ ( approximately 2 weeks, compared with only hours for the comparable IgG complex) contributes to the permanent sensitization of these cells and, hence, to the immediate response to allergens. Here we show that the second constant domain of IgE, Cepsilon2, which takes the place of the flexible hinge in IgG, contributes to this long half-life. When the Cepsilon2 domain is deleted from the IgE Fc fragment, leaving only the Cepsilon3 and Cepsilon4 domains (Cepsilon3-4 fragment), the rate of dissociation from the receptor is increased by greater than 1 order of magnitude. We report the structure of the Cepsilon2 domain by heteronuclear NMR spectroscopy and show by chemical shift perturbation that it interacts with FcepsilonRIalpha. By sedimentation equilibrium we show that the Cepsilon2 domain binds to the Cepsilon3-4 fragment of IgE. These interactions of Cepsilon2 with both FcepsilonRIalpha and Cepsilon3-4 provide a structural explanation for the exceptionally slow dissociation of the IgE-FcepsilonRIalpha complex.

Citations

Dec 26, 2002·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Oct 23, 2008·Cancer Immunology, Immunotherapy : CII·Panagiotis KaragiannisSophia N Karagiannis
Jun 8, 2012·Cancer Immunology, Immunotherapy : CII·Edzard SpillnerIngke Braren
May 15, 2002·Immunology Letters·Peter Sondermann, Vaughan Oosthuizen
Apr 28, 2011·Biochemistry·Susmita BorthakurJames M McDonnell
Mar 26, 2004·Nature Reviews. Immunology·Jenny M Woof, Dennis R Burton
Feb 28, 2008·Nature Reviews. Immunology·Hannah J Gould, Brian J Sutton
Apr 26, 2011·Nature Structural & Molecular Biology·Mary D HoldomBrian J Sutton
Jul 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Balvinder DhaliwalBrian J Sutton
Jul 14, 2009·The Journal of Biological Chemistry·Alexander I TaylorRosaleen A Calvert
Sep 21, 2005·The Journal of Experimental Medicine·Richard G HibbertJames M McDonnell
Dec 26, 2002·Annual Review of Immunology·Hannah J GouldLyn Smurthwaite
Mar 19, 2014·Nature Structural & Molecular Biology·Nyssa DrinkwaterBrian J Sutton
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Roger MüllerJohannes Buchner
Apr 3, 2014·Veterinary Immunology and Immunopathology·R C EldersB Catchpole
Jun 28, 2002·Nature Immunology·Natalija Novak, Thomas Bieber
Jun 18, 2002·Nature Immunology·Tommy WanBrian J Sutton
May 4, 2011·Journal of Peptide Science : an Official Publication of the European Peptide Society·Annamaria SandomenicoMenotti Ruvo
Apr 11, 2008·The Journal of Biological Chemistry·Alexander I TaylorRosaleen A Calvert
Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christian LupinekRudolf Valenta
Jan 27, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eva UntersmayrErika Jensen-Jarolim
Nov 3, 2004·The Journal of Biological Chemistry·Naomi E PriceJames M McDonnell
Mar 4, 2005·The Journal of Biological Chemistry·James HuntAndrew J Beavil
Feb 29, 2020·Biomolecular NMR Assignments·Stefi V BenjaminJames M McDonnell
Jan 11, 2005·The American Journal of Clinical Nutrition·Isabella SchöllErika Jensen-Jarolim
Aug 23, 2018·Frontiers in Immunology·Abulikemu AbudukelimuHans V Westerhoff
Oct 27, 2015·Immunological Reviews·Brian J Sutton, Anna M Davies
Jan 19, 2005·The FEBS Journal·Aalt D J van DijkAlexandre M J J Bonvin
Apr 17, 2002·Molecular Immunology·Beth A Wurzburg, Theodore S Jardetzky
Jul 7, 2012·The Journal of Allergy and Clinical Immunology·Sandy R DurraniDaniel J Jackson
May 18, 2021·Allergy·Mohamed H ShamjiR J Joost van Neerven
Dec 26, 2006·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Naomi E Harwood, James M McDonnell
Sep 23, 2021·Clinical Reviews in Allergy & Immunology·Laurent GuilleminaultLaurent Lionel Reber
Aug 25, 2009·Molecular Immunology·Annamaria SandomenicoMenotti Ruvo
Sep 8, 2009·Developmental and Comparative Immunology·Alexander I TaylorRosaleen A Calvert

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