SASDC76: Extracellular domain of human B-lymphocyte cell receptor CD22

Basic information

• Entry: Database: SASBDB / ID: SASDC76

Sample

Extracellular domain of human B-lymphocyte cell receptor CD22

• CD22 extracellular domain (protein), CD22, Homo sapiens

Function / homology

Function:

regulation of B cell proliferation / IgM binding / negative regulation of immunoglobulin production / negative regulation of B cell receptor signaling pathway / sialic acid binding / CD22 mediated BCR regulation / CD4 receptor binding / negative regulation of calcium-mediated signaling / neuronal cell body membrane / B cell activation / regulation of endocytosis / regulation of immune response / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / recycling endosome / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / carbohydrate binding / protein phosphatase binding / early endosome / cell adhesion / external side of plasma membrane / signaling receptor binding / cell surface / extracellular exosome / membrane / plasma membrane / cytoplasm

Domain/homology:

CD80-like, immunoglobulin C2-set / CD80-like C2-set immunoglobulin domain / Immunoglobulin domain / Immunoglobulin domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold

Component:

B-cell receptor CD22

• Biological species: Homo sapiens (human)
• Citation: Journal: Nat Commun / Year: 2017; Title: Molecular basis of human CD22 function and therapeutic targeting.; Authors: June Ereño-Orbea / Taylor Sicard / Hong Cui / Mohammad T Mazhab-Jafari / Samir Benlekbir / Alba Guarné / John L Rubinstein / Jean-Philippe Julien / ; Abstract: 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 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-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 Å 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.

Contact author

• June Ereno Orbea (the hospital for sick children)

Models

• Model #1404: ; Type: dummy / Radius of dummy atoms: 5.25 A / Chi-square value: 0.416; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Extracellular domain of human B-lymphocyte cell receptor CD22; Specimen concentration: 5.00-5.00
• Buffer: Name: 20 mM Tris 150 mM NaCl / pH: 9

Entity #744

Name: CD22 / Type: protein / Description: CD22 extracellular domain / Formula weight: 90 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P20273
Sequence:

MSLWLLEGVP MRQAAVTSTS LTIKSVFTRS ELKFSPQWSH HGKIVTCQLQ DADGKFLSND TVQLNVKHTP KLEIKVTPSD AIVREGDSVT MTCEVSSSNP EYTTVSWLKD GTSLKKQNTF TLNLREVTKD QSGKYCCQVS NDVGPGRSEE VFLQVQYAPE PSTVQILHSP AVEGSQVEFL CMSLANPLPT NYTWYHNGKE MQGRTEEKVH IPKILPWHAG TYSCVAENIL GTGQRGPGAE LDVQYPPKKV TTVIQNPMPI REGDTVTLSC NYNSSNPSVT RYEWKPHGAW EEPSLGVLKI QNVGWDNTTI ACAACNSWCS WASPVALNVQ YAPRDVRVRK IKPLSEIHSG NSVSLQCDFS SSHPKEVQFF WEKNGRLLGK ESQLNFDSIS PEDAGSYSCW VNNSIGQTAS KAWTLEVLYA PRRLRVSMSP GDQVMEGKSA TLTCESDANP PVSHYTWFDW NNQSLPYHSQ KLRLEPVKVQ HSGAYWCQGT NSVGKGRSPL STLTVYYSPE TIGRRVAVGL GSCLAILILA ICGLKLQRRW KRTQSQQGLQ ENSSGQSFFV RNKKVRRAPL SEGPHSLGCY NPMMEDGISY TTLRFPEMNI PRTGDAESSE MQRPPPDCDD TVTYSALHKR QVGDYENVIP DFPEDEGIHY SELIQFGVGE RPQAQENVDY VILKHHHHHH H

Experimental information

• Beam: Instrument name: Advanced Photon Source (APS) 12ID-B SAXS/WAXS; City: Argonne, IL / 国: USA / Type of source: X-ray synchrotron / Wavelength: 0.0886 Å / Dist. spec. to detc.: 3.6 mm
• Detector: Name: Pilatus 2M

Scan

Title: Extracellular domain of human B-lymphocyte cell receptor CD22
Measurement date: Apr 21, 2016 / Cell temperature: 22 °C / Exposure time: 1 sec. / Number of frames: 30 / Unit: 1/A /

	Min	Max
Q	0.0082	0.516

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 147 /

	Min	Max
Q	0.009274	0.202
P(R) point	1	147
R	0	305.7

Result

Experimental MW: 90 kDa / Type of curve: single_conc

	P(R)	Guinier	Guinier error
Forward scattering, I0	0.3495	0.346495	-
Radius of gyration, Rg	8.426 nm	8.005 nm	0.63

	Min	Max
D	-	30.57
Guinier point	2	20