The Fc segment of IgE influences the kinetics of dissociation of a symmetrical bivalent ligand from cyclic dimeric complexes

Biochemistry
K SubramanianB Goldstein

Abstract

As part of a systematic effort to determine the features of immunoglobulin E-receptor (IgE-Fc epsilon RI) aggregation that are critical for cellular activation, we used fluorescence to examine the dissociation of a soluble bivalent ligand, N, N'-bis[[epsilon-[(2,4-dinitrophenyl)amino]caproyl]-L-tyrosyl]-L-cystine ((DCT)2-cys), from soluble bivalent IgE and its bivalent F(ab')2 and monovalent Fab' fragments. Cross-linking of Fab' fragments by (DCT)2-cys is limited to linear dimers, and we find that (DCT)2-cys dissociation from Fab' occurs with a single kinetic coefficient [(4.2 +/- 0.6) x 10-3 s-1] that corresponds to the lower of the two kinetic coefficients observed with the bivalent IgE [(4.7 +/- 0.7) x 10-2 s-1 and (4.4 +/- 0.3) x 10-3 s-1]. Similarly, the lower value is obtained for dissociation of (DCT)2-cys that is monovalently bound to IgE after incubation with a large excess of the ligand. (DCT)2-cys can bind to bivalent F(ab')2 fragments and form a variety of linear and cyclic aggregates, similarly to IgE, but, unlike IgE, we find that dissociation occurs with a single kinetic coefficient similar to that observed for Fab'. We find that IgE and its (Fab')2 fragments form highly stable cyclic dimer rings with two (DCT)2-...Continue Reading

Citations

Mar 1, 2007·Journal of the American Chemical Society·Basar BilgiçerGeorge M Whitesides
Nov 18, 2011·Journal of the American Chemical Society·Eric T MackGeorge M Whitesides
Jun 19, 2009·Journal of the American Chemical Society·Başar BilgiçerGeorge M Whitesides
Sep 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Min WuBarbara Baird
Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Alexis J TorresBarbara A Baird
Jun 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·W S HlavacekB Goldstein
May 15, 2007·Immunological Reviews·David HolowkaBarbara Baird
Apr 10, 2003·Journal of the American Chemical Society·Emma L DoyleNicholas H Williams

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