Behavior of glycolylated sialoglycans in the binding pockets of murine and human CD22

Cristina Di Carluccio; Rosa Ester Forgione; Marco Montefiori; Monica Civera; Sara Sattin; Giovanni Smaldone; K Fukase; Y Manabe; Paul R Crocker; Antonio Molinaro; Roberta Marchetti; Alba Silipo

doi:10.1016/j.isci.2020.101998

Behavior of glycolylated sialoglycans in the binding pockets of murine and human CD22

iScience. 2020 Dec 29;24(1):101998. doi: 10.1016/j.isci.2020.101998. eCollection 2021 Jan 22.

Authors

Affiliations

¹ Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, 80126 Napoli, Italy.
² Dipartimento di Chimica, Università Degli Studi di Milano, Via Golgi, 19, 20133 Milano, Italy.
³ IRCCS SDN, Via E. Gianturco 113, Napoli, Italy.
⁴ Department of Chemistry, Graduate School of Science, Osaka University, Suita, Japan.
⁵ Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.

Abstract

Siglecs (sialic acid binding immunoglobulin (Ig)-like lectins) constitute a group of 15 human and 9 murine cell-surface transmembrane receptors belonging to the I-type lectin family, mostly expressed on innate immune cells and characterized by broadly similar structural features. Here, the prominent inhibitory CD22 (Siglec-2), well known in maintaining tolerance and preventing autoimmune responses on B cells, is studied in its human and murine forms in complex with sialoglycans. In detail, the role of the N-glycolyl neuraminic acid (Neu5Gc) moiety in the interaction with both orthologues was explored. The analysis of the binding mode was carried out by the combination of NMR spectroscopy, computational approaches, and CORCEMA-ST calculations. Our findings provide a first model of Neu5Gc recognition by h-CD22 and show a comparable molecular recognition profile by h- and m-CD22. These data open the way to innovative diagnostic and/or therapeutic methodologies to be used in the modulation of the immune responses.

Keywords: Biochemistry; Immunology; Structural Biology.