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, Roberta Marchetti, Alba Silipo

Research output: Contribution to journalArticle

1 Citation (Scopus)

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
JournalChemBioChem
Early online date16 May 2019
DOIs
Publication statusE-pub ahead of print - 16 May 2019

Fingerprint

Sialic Acid Binding Ig-like Lectin 2
Polysaccharides
B-Lymphocytes
Cells
Autoantigens
N-Acetylneuraminic Acid
Computational methods
Autoimmunity
Galactose
Oligomers
Nuclear magnetic resonance spectroscopy
Autoimmune Diseases
Assays
Membrane Proteins
Magnetic Resonance Spectroscopy
Neoplasms
Proteins
Therapeutics

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., ... Silipo, A. (2019). Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22. ChemBioChem. https://doi.org/10.1002/cbic.201900295
Di Carluccio, Cristina ; Crisman, Enrique ; Manabe, Yoshiyuki ; Forgione, Rosa Ester ; Lacetera, Alessandra ; Amato, Jussara ; Pagano, Bruno ; Randazzo, Antonio ; Zampella, Angela ; Lanzetta, Rosa ; Fukase, Koichi ; Molinaro, Antonio ; Crocker, Paul R. ; Martín-Santamaría, Sonsoles ; Marchetti, Roberta ; Silipo, Alba. / Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22. In: ChemBioChem. 2019.
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title = "Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22",
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.",
keywords = "molecular recognition, N-glycans, NMR spectroscopy, sialic acids, Siglecs",
author = "{Di Carluccio}, Cristina and Enrique Crisman and Yoshiyuki Manabe and Forgione, {Rosa Ester} and Alessandra Lacetera and Jussara Amato and Bruno Pagano and Antonio Randazzo and Angela Zampella and Rosa Lanzetta and Koichi Fukase and Antonio Molinaro and Crocker, {Paul R.} and Sonsoles Mart{\'i}n-Santamar{\'i}a and Roberta Marchetti and Alba Silipo",
note = "Funding Information H2020 Marie Skłodowska-Curie Actions. Grant Numbers: 642157, 814102 Mizutani Foundation for Glycoscience. Grant Number: 2014-2015",
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Di Carluccio, C, Crisman, E, Manabe, Y, Forgione, RE, Lacetera, A, Amato, J, Pagano, B, Randazzo, A, Zampella, A, Lanzetta, R, Fukase, K, Molinaro, A, Crocker, PR, Martín-Santamaría, S, Marchetti, R & Silipo, A 2019, 'Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22', ChemBioChem. https://doi.org/10.1002/cbic.201900295

Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22. / Di Carluccio, Cristina; Crisman, Enrique; Manabe, Yoshiyuki; Forgione, Rosa Ester; Lacetera, Alessandra; Amato, Jussara; Pagano, Bruno; Randazzo, Antonio; Zampella, Angela; Lanzetta, Rosa; Fukase, Koichi; Molinaro, Antonio; Crocker, Paul R.; Martín-Santamaría, Sonsoles; Marchetti, Roberta; Silipo, Alba.

In: ChemBioChem, 16.05.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22

AU - Di Carluccio, Cristina

AU - Crisman, Enrique

AU - Manabe, Yoshiyuki

AU - Forgione, Rosa Ester

AU - Lacetera, Alessandra

AU - Amato, Jussara

AU - Pagano, Bruno

AU - Randazzo, Antonio

AU - Zampella, Angela

AU - Lanzetta, Rosa

AU - Fukase, Koichi

AU - Molinaro, Antonio

AU - Crocker, Paul R.

AU - Martín-Santamaría, Sonsoles

AU - Marchetti, Roberta

AU - Silipo, Alba

N1 - Funding Information H2020 Marie Skłodowska-Curie Actions. Grant Numbers: 642157, 814102 Mizutani Foundation for Glycoscience. Grant Number: 2014-2015

PY - 2019/5/16

Y1 - 2019/5/16

N2 - 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.

AB - 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.

KW - molecular recognition

KW - N-glycans

KW - NMR spectroscopy

KW - sialic acids

KW - Siglecs

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U2 - 10.1002/cbic.201900295

DO - 10.1002/cbic.201900295

M3 - Article

C2 - 31095840

AN - SCOPUS:85074393287

JO - ChemBioChem

JF - ChemBioChem

SN - 1439-4227

ER -

Di Carluccio C, Crisman E, Manabe Y, Forgione RE, Lacetera A, Amato J et al. Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22. ChemBioChem. 2019 May 16. https://doi.org/10.1002/cbic.201900295