Behavior of glycolylated sialoglycans in the binding pockets of murine and human CD22.
Behavior of glycolylated sialoglycans in the binding pockets of murine and human CD22.
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DOI：
10.1016/j.isci.2020.101998
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发表时间：
2021-01-22
期刊：
影响因子：
5.8
通讯作者：
Silipo A
中科院分区：
文献类型：
--
作者：
Di Carluccio C;Forgione RE;Montefiori M;Civera M;Sattin S;Smaldone G;Fukase K;Manabe Y;Crocker PR;Molinaro A;Marchetti R;Silipo A
Siglecs(唾液酸结合免疫球蛋白(Ig)样凝集素)由15个人和9个小鼠细胞表面跨膜受体组成，属于I型凝集素家族，主要表达在天然免疫细胞上，具有广泛相似的结构特征。在这里，突出的抑制性CD22(Siglec-2)，众所周知，在维持耐受性和防止B细胞的自身免疫反应中，以人和鼠的形式与唾液酸聚糖复合体进行了研究。详细地，探讨了N-羟基神经氨酸(Neu5Gc)部分在与两个同源物相互作用中的作用。结合核磁共振波谱、计算方法和CORCEMA-ST计算对结合模式进行了分析。我们的发现提供了h-CD22识别Neu5Gc的第一个模型，并显示了h-和m-CD22类似的分子识别图谱。这些数据为用于调节免疫反应的创新诊断和/或治疗方法开辟了道路。本文研究了h/mCD22识别唾液酸的结构基础，比较了含Neu5Gc/Neu5Ac的配体与m/h-CD22的结合方式，推测了唾液酸聚糖的生物活性构象。我们的发现有助于免疫反应的调节和癌症的预防。
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. The structural basis of sialoglycans recognition by h/m CD22 has been investigated The binding modes of Neu5Gc-/Neu5Ac-containing ligands to m/h-CD22 were compared The bioactive conformation of sialoglycans has been derived Our findings may help in the regulation of immune response and cancer prevention Biochemistry; Immunology; Structural Biology
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影响因子：
8.7
作者：
Mahajan VS;Pillai S
通讯作者：
Pillai S
影响因子：
3
作者：
Morris, Garrett M.;Huey, Ruth;Lindstrom, William;Sanner, Michel F.;Belew, Richard K.;Goodsell, David S.;Olson, Arthur J.
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通讯作者：
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