Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular basis of human CD22 function and therapeutic targeting.
Journal, issue, pages	Nat Commun, Vol. 8, Issue 1, Page 764, Year 2017
Publish date	Oct 2, 2017
Authors	June Ereño-Orbea / Taylor Sicard / Hong Cui / Mohammad T Mazhab-Jafari / Samir Benlekbir / Alba Guarné / John L Rubinstein / Jean-Philippe Julien /
PubMed 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 ...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.
External links	Nat Commun / PubMed:28970495 / PubMed Central
Methods	SAS (X-ray synchrotron) / EM (single particle) / X-ray diffraction
Resolution	2.014 - 30.0 Å
Structure data	SASDC76: Extracellular domain of human B-lymphocyte cell receptor CD22 Method: SAXS/SANS SASDC86: Extracellular domain of human B-lymphocyte cell receptor CD22 in complex with alpha 2,6 sialyllactose Method: SAXS/SANS EMDB-8704: Negative stain electron microscopy map of human CD22 extracellular domain Method: EM (single particle) / Resolution: 30.0 Å EMDB-8705: Negative stain electron microscopy map of human CD22 extracellular domain in complex with epratuzumab Fab Method: EM (single particle) / Resolution: 30.0 Å PDB-5vkj: Crystal structure of human CD22 Ig domains 1-3 Method: X-RAY DIFFRACTION / Resolution: 2.12 Å PDB-5vkk: Crystal structure of Fab fragment of anti-CD22 Epratuzumab Method: X-RAY DIFFRACTION / Resolution: 2.014 Å PDB-5vkm: Crystal structure of human CD22 Ig domains 1-3 in complex with alpha 2-6 sialyllactose Method: X-RAY DIFFRACTION / Resolution: 2.2 Å PDB-5vl3: CD22 d1-d3 in complex with therapeutic Fab Epratuzumab Method: X-RAY DIFFRACTION / Resolution: 3.1 Å
Chemicals	ChemComp-GOL: GLYCEROL ChemComp-HOH: WATER
Source	homo sapiens (human) mus musculus (house mouse)
Keywords	IMMUNE SYSTEM / Siglec / Sialic acid / carbohydrate binding protein / therapeutic antibody / B cell / Fab