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Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22 |
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| Authors: | Cristina Di Carluccio Enrique Crisman Prof. Yoshiyuki Manabe Rosa Ester Forgione Dr. Alessandra Lacetera Dr. Jussara Amato Dr. Bruno Pagano Prof. Antonio Randazzo Prof. Angela Zampella Prof. Rosa Lanzetta Prof. Koichi Fukase Prof. Antonio Molinaro Prof. Paul R. Crocker Prof. Sonsoles Martín-Santamaría Dr. Roberta Marchetti Prof. Alba Silipo |
| Affiliation: | 1. Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, 80126 Napoli, Italy;2. Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas, CIB-CSIC, C/Ramiro de Maeztu, 9, 28040 Madrid, Spain;3. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan Core for Medicine and Science Collaborative Research and Education, Project Research Center for Fundamental Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan;4. Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy;5. Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, 80126 Napoli, Italy Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan;6. Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK |
| 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 |