6al5
COMPLEX BETWEEN CD19 (N138Q MUTANT) AND B43 FAB
Structural highlights
DiseaseCD19_HUMAN Common variable immunodeficiency. The disease is caused by mutations affecting the gene represented in this entry. FunctionCD19_HUMAN Assembles with the antigen receptor of B-lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation. Publication Abstract from PubMedCD19 is a transmembrane protein expressed on malignant B cells, but not in other lineages or other tissues, which makes it an attractive target for monoclonal antibody-mediated immunotherapy. Anti-CD19 antibody B43 was utilized in a bispecific T-cell engager (BiTE) blinatumomab that demonstrated potency for the treatment of relapsed acute lymphoblastic leukemia. To gain insight into the mechanism of action of the antibody, the crystal structure of B43 Fab was determined in complex with CD19 and in the unbound form. The structure revealed the binding epitope, explained the lack of cross-reactivity toward non-human species, and suggested the key-and-lock mechanism of antigen recognition. Most unexpectedly, the structure revealed a unique molecular topology of CD19. Rather than a tandem of c-type immunoglobulin folds predicted from the amino acid sequence, the extracellular domain of CD19 exhibits an elongated beta-sandwich formed by two immunoglobulin folds by swapping their C-terminal halves. This is the first structure of CD19, which has no sequence homologs. Crystal structure of B-cell co-receptor CD19 in complex with antibody B43 reveals an unexpected fold.,Teplyakov A, Obmolova G, Luo J, Gilliland GL Proteins. 2018 Feb 28. doi: 10.1002/prot.25485. PMID:29490423[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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