Analysis of IgA1 N-glycosylation and its contribution to FcαRI binding

Michelle M. Gomes, Stephanie B. Wall, Kazuo Takahashi, Jan Novak, Matthew B. Renfrow, Andrew B. Herr

Research output: Contribution to journalArticle

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Abstract

The IgA isotype of human antibodies triggers inflammatory responses via the IgA-specific receptor FcαRI (CD89). Structural studies have suggested that IgA1 N-glycans could modulate the interaction with FcαRI. We have carried out detailed biophysical analyses of three IgA1 samples purified from human serum and recombinant IgA1-Fc and compared their binding to FcαRI. Analytical ultracentrifugation revealed wide variation in the distribution of polymeric species between IgA1 samples, and Fourier transform ion cyclotron resonance mass spectrometry showed overlapping but distinct populations of N-glycan species between IgA1 samples. Kinetic and equilibrium data from surface plasmon resonance experiments revealed that variation in the IgA1 C H2 N-glycans had no effect on the kinetics or affinity constants for binding to FcαRI. Indeed, complete enzymatic removal of the IgA1 N-glycans yielded superimposable binding curves. These findings have implications for renal diseases such as IgA nephropathy.

Original languageEnglish
Pages (from-to)11285-11299
Number of pages15
JournalBiochemistry
Volume47
Issue number43
DOIs
Publication statusPublished - 28-10-2008

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Glycosylation
Immunoglobulin A
Polysaccharides
Cyclotrons
Surface Plasmon Resonance
Cyclotron resonance
Ultracentrifugation
Kinetics
Fourier Analysis
Surface plasmon resonance
Mass Spectrometry
Mass spectrometry
Fourier transforms
Ions
Kidney

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Gomes, M. M., Wall, S. B., Takahashi, K., Novak, J., Renfrow, M. B., & Herr, A. B. (2008). Analysis of IgA1 N-glycosylation and its contribution to FcαRI binding. Biochemistry, 47(43), 11285-11299. https://doi.org/10.1021/bi801185b
Gomes, Michelle M. ; Wall, Stephanie B. ; Takahashi, Kazuo ; Novak, Jan ; Renfrow, Matthew B. ; Herr, Andrew B. / Analysis of IgA1 N-glycosylation and its contribution to FcαRI binding. In: Biochemistry. 2008 ; Vol. 47, No. 43. pp. 11285-11299.
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Gomes, MM, Wall, SB, Takahashi, K, Novak, J, Renfrow, MB & Herr, AB 2008, 'Analysis of IgA1 N-glycosylation and its contribution to FcαRI binding', Biochemistry, vol. 47, no. 43, pp. 11285-11299. https://doi.org/10.1021/bi801185b

Analysis of IgA1 N-glycosylation and its contribution to FcαRI binding. / Gomes, Michelle M.; Wall, Stephanie B.; Takahashi, Kazuo; Novak, Jan; Renfrow, Matthew B.; Herr, Andrew B.

In: Biochemistry, Vol. 47, No. 43, 28.10.2008, p. 11285-11299.

Research output: Contribution to journalArticle

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