5TLK

COMPLEX BETWEEN HUMAN CD27 AND FAB FRAGMENTS OF ANTIBODIES M2177 AND H2191

Summary for 5TLK

• Entry DOI: 10.2210/pdb5tlk/pdb
• Related: 5TL5 5TLJ
• Descriptor: M2177 LIGHT CHAIN, M2177 HEAVY CHAIN, H2191 LIGHT CHAIN, ... (7 entities in total)
• Functional Keywords: immune system
• Biological source: Mus musculus, Homo sapiens (Mouse, Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P26842
• Total number of polymer chains: 10
• Total formula weight: 218117.00

Authors

Teplyakov, A.,Obmolova, G.,Malia, T.,Gilliland, G.L. (deposition date: 2016-10-11, release date: 2017-02-08, Last modification date: 2024-10-23)

Primary citation

Obmolova, G.,Teplyakov, A.,Malia, T.J.,Wunderler, N.,Kwok, D.,Barone, L.,Sweet, R.,Ort, T.,Scully, M.,Gilliland, G.L.
Epitope-dependent mechanisms of CD27 neutralization revealed by X-ray crystallography.
Mol. Immunol., 83:92-99, 2017

PubMed Abstract: 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-κB 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.

PubMed: 28119207
DOI: 10.1016/j.molimm.2017.01.005

Experimental method

X-RAY DIFFRACTION (2.7 Å)