Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22

Cristina Di Carluccio, Enrique Crisman, Yoshiyuki Manabe, Rosa Ester Forgione, Alessandra Lacetera, Jussara Amato, Bruno Pagano, Antonio Randazzo, Angela Zampella, Rosa Lanzetta, Koichi Fukase, Antonio Molinaro, Paul R. Crocker, Sonsoles Martín-Santamaría (Lead / Corresponding author), Roberta Marchetti (Lead / Corresponding author), Alba Silipo (Lead / Corresponding author)

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Abstract

CD22 (Siglec-2) is a B-cell surface inhibitory protein capable of selectively recognising sialylated glycans, thus dampening autoimmune responses against self-antigens. Here we have characterised the dynamic recognition of complex-type N-glycans by human CD22 by means of orthogonal approaches including NMR spectroscopy, computational methods and biophysical assays. We provide new molecular insights into the binding mode of sialoglycans in complex with h-CD22, highlighting the role of the sialic acid galactose moieties in the recognition process, elucidating the conformational behaviour of complex-type N-glycans bound to Siglec-2 and dissecting the formation of CD22 homo-oligomers on the B-cell surface. Our results could enable the development of additional therapeutics capable of modulating the activity of h-CD22 in autoimmune diseases and malignancies derived from B-cells.

Original languageEnglish
Pages (from-to)129-140
Number of pages12
JournalChemBioChem
Volume21
Issue number1-2
Early online date16 May 2019
DOIs
Publication statusPublished - 15 Jan 2020

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Keywords

  • molecular recognition
  • N-glycans
  • NMR spectroscopy
  • sialic acids
  • Siglecs

Cite this

Di Carluccio, C., Crisman, E., Manabe, Y., Forgione, R. E., Lacetera, A., Amato, J., Pagano, B., Randazzo, A., Zampella, A., Lanzetta, R., Fukase, K., Molinaro, A., Crocker, P. R., Martín-Santamaría, S., Marchetti, R., & Silipo, A. (2020). Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22. ChemBioChem, 21(1-2), 129-140. https://doi.org/10.1002/cbic.201900295