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5vkm

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Revision as of 16:55, 20 November 2019

Crystal structure of human CD22 Ig domains 1-3 in complex with alpha 2-6 sialyllactose

Structural highlights

5vkm is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Related:	5vkj, 5vkk, 5vl3
Gene:	CD22, SIGLEC2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CD22_HUMAN] Mediates B-cell B-cell interactions. May be involved in the localization of B-cells in lymphoid tissues. Binds sialylated glycoproteins; one of which is CD45. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site can be masked by cis interactions with sialic acids on the same cell surface. Upon ligand induced tyrosine phosphorylation in the immune response seems to be involved in regulation of B-cell antigen receptor signaling. Plays a role in positive regulation through interaction with Src family tyrosine kinases and may also act as an inhibitory receptor by recruiting cytoplasmic phosphatases via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules.

Publication Abstract from PubMed

CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers. Here we report the crystal structure of human CD22 at 2.1 A resolution, which reveals that specificity for alpha2-6 sialic acid ligands is dictated by a pre-formed beta-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins. The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals. We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 A resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement. Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells. Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.

Molecular basis of human CD22 function and therapeutic targeting.,Ereno-Orbea J, Sicard T, Cui H, Mazhab-Jafari MT, Benlekbir S, Guarne A, Rubinstein JL, Julien JP Nat Commun. 2017 Oct 2;8(1):764. doi: 10.1038/s41467-017-00836-6. PMID:28970495^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ereno-Orbea J, Sicard T, Cui H, Mazhab-Jafari MT, Benlekbir S, Guarne A, Rubinstein JL, Julien JP. Molecular basis of human CD22 function and therapeutic targeting. Nat Commun. 2017 Oct 2;8(1):764. doi: 10.1038/s41467-017-00836-6. PMID:28970495 doi:http://dx.doi.org/10.1038/s41467-017-00836-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5vkm"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human CD22 Ig domains 1-3 in complex with alpha 2-6 sialyllactose==
-<StructureSection load='5vkm' size='340' side='right' caption='[[5vkm]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='5vkm' size='340' side='right'caption='[[5vkm]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5vkm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VKM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5vkm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VKM FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vkj|5vkj]], [[5vkk|5vkk]], [[5vl3|5vl3]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD22, SIGLEC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vkm OCA], [http://pdbe.org/5vkm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vkm RCSB], [http://www.ebi.ac.uk/pdbsum/5vkm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vkm ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Ereno-Orbea, J]]
 [[Category: Julien, J P]]

5vkm

From Proteopedia

Revision as of 16:55, 20 November 2019

Crystal structure of human CD22 Ig domains 1-3 in complex with alpha 2-6 sialyllactose

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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