TY - JOUR
T1 - Behavior of glycolylated sialoglycans in the binding pockets of murine and human CD22
AU - Di Carluccio, Cristina
AU - Forgione, Rosa Ester
AU - Montefiori, Marco
AU - Civera, Monica
AU - Sattin, Sara
AU - Smaldone, Giovanni
AU - Fukase, K.
AU - Manabe, Y.
AU - Crocker, Paul R.
AU - Molinaro, Antonio
AU - Marchetti, Roberta
AU - Silipo, Alba
N1 - Funding Information:
This study was supported by PRIN 2017 “Glytunes” ( 2017XZ2ZBK , 2019-2022) to AS and SS; progetto POR SATIN and Progetto POR Campania Oncoterapia to AM; the European Commission ( H2020-MSCA- 814102 --SWEET CROSSTALK project) to AM, RM, and AS; and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program under grant agreement No 851356 to RM. PON Ricerca e Innovazione 2014-2020 , Azione I.1 “ Dottorati Innovativi con caratterizzazione Industriale ” is acknowledged for funding the Ph.D. grant to R.E.F.
Publisher Copyright:
© 2020 The Author(s)
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/22
Y1 - 2021/1/22
N2 - 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.
AB - 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.
KW - Biochemistry
KW - Immunology
KW - Structural Biology
UR - http://www.scopus.com/inward/record.url?scp=85099251039&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2020.101998
DO - 10.1016/j.isci.2020.101998
M3 - Article
C2 - 33490906
AN - SCOPUS:85099251039
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 1
M1 - 101998
ER -