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CD22 (Siglec-2) is a B-cell surface inhibitory protein able to selectively recognize sialylated glycans, dampening autoimmune responses against self-antigens. We here characterize 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 novel 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 will enable the development of additional therapeutics able to modulate the activity of h-CD22 in autoimmune diseases and B-cell derived malignancies.
This article was published in the following journal.
Name: Chembiochem : a European journal of chemical biology
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Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
A lectin and cell adhesion molecule found in B-LYMPHOCYTES. It interacts with SIALIC ACIDS and mediates signaling from B-CELL ANTIGEN RECEPTORS.
The interactions of particles responsible for their scattering and transformations (decays and reactions). Because of interactions, an isolated particle may decay into other particles. Two particles passing near each other may transform, perhaps into the same particles but with changed momenta (elastic scattering) or into other particles (inelastic scattering). Interactions fall into three groups: strong, electromagnetic, and weak. (From McGraw-Hill Encyclopedia of Science & Technology, 7th ed)
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. T8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
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