5tlk
From Proteopedia
COMPLEX BETWEEN HUMAN CD27 AND FAB FRAGMENTS OF ANTIBODIES M2177 AND H2191
Structural highlights
DiseaseCD27_HUMAN Autosomal recessive lymphoproliferative disease. The disease is caused by mutations affecting the gene represented in this entry. FunctionCD27_HUMAN Receptor for CD70/CD27L. May play a role in survival of activated T-cells. May play a role in apoptosis through association with SIVA1. Publication Abstract from PubMedCD27 is a T and B cell co-stimulatory protein of the TNF receptor superfamily dependent on the availability of the TNF-like ligand CD70. Two anti-CD27 neutralizing monoclonal antibodies were obtained from mouse hybridoma and subsequently humanized and optimized for binding the target. The two antibodies are similar in terms of their CD27-binding affinity and ability to block NF-kappaB signaling, however their clearance rates in monkeys are very different. The pharmacokinetics profiles could be epitope dependent. To identify the epitopes, we determined the crystal structure of the ternary complex between CD27 and the Fab fragments of these non-competing antibodies. The structure reveals the binding modes of the antibodies suggesting that their mechanisms of action are distinctly different and provides a possible explanation of the in vivo data. Epitope-dependent mechanisms of CD27 neutralization revealed by X-ray crystallography.,Obmolova G, Teplyakov A, Malia TJ, Wunderler N, Kwok D, Barone L, Sweet R, Ort T, Scully M, Gilliland GL Mol Immunol. 2017 Mar;83:92-99. doi: 10.1016/j.molimm.2017.01.005. Epub 2017 Jan , 21. PMID:28119207[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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