CANADIAN MACROMOLECULAR CRYSTALLOGRAPHY FACILITY

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TACKLING AUTOIMMUNE DISEASES

Researchers combine CMCF-BM, CMCF-ID, SAXS & electron microscopy data to discover B-cell CD22 interaction details critical to a healthy immune response...

Oct. 11, 2017

CD22 is a B-cell surface protein involved in regulating the immune response. CD22 knockout mice, for example, have a higher rate of autoimmune disease. CD22's role has been known for some time, but a detailed molecular understanding has been lacking. Now, researchers from the University of Toronto and Hospital for Sick Children (SickKids) have presented a detailed structural model of this key immune component.

Combining X-ray crystallography, SAXS and electron microscopy, the researchers describe the molecular structure of human CD22 alone as well as in complex with a sialyllactose ligand or a therapeutic antibody. Initial crystallographic phasing of a portion of CD22 was accomplished by performing a Hg-MAD experiment on beamline CMCF-BM. The resulting structure allowed solution of the structures of the complexes, for which date were obtained on beamline CMCF-ID. SAXS and electron microscopy data rounded out the picture with the result being a description of the full-length extracellular portion of CD22. The work provides key information about the mechanisms controlling B-cell inhibition and clues for designing new autoimmune therapies. PDB ID 5VKJ

Nature Commun. 8, 764