5tlj

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COMPLEX BETWEEN HUMAN CD27 AND FAB FRAGMENTS OF ANTIBODIES M2177 AND M2191

Structural highlights

5tlj is a 9 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.5Å
Ligands:NAG, PCA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CD27_HUMAN Autosomal recessive lymphoproliferative disease. The disease is caused by mutations affecting the gene represented in this entry.

Function

CD27_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 PubMed

CD27 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.

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Citations
0 reviews cite this structure
Preclinical characterization and clinical translation of pharmacodynamic markers for MK-5890: a human CD27 activating antibody for cancer immunotherapy.
Guelen et al. (2022)
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1 other articles
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See Also

References

  1. ↑ Obmolova G, Teplyakov A, Malia TJ, Wunderler N, Kwok D, Barone L, Sweet R, Ort T, Scully M, Gilliland GL. Epitope-dependent mechanisms of CD27 neutralization revealed by X-ray crystallography. Mol Immunol. 2017 Mar;83:92-99. doi: 10.1016/j.molimm.2017.01.005. Epub 2017 Jan , 21. PMID:28119207 doi:http://dx.doi.org/10.1016/j.molimm.2017.01.005

Contents


PDB ID 5tlj

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OCA

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