6K0Y

Study of the interactions of a novel monoclonal antibody, mAb059c, with the hPD-1 receptor

Summary for 6K0Y

• Entry DOI: 10.2210/pdb6k0y/pdb
• Descriptor: Antibody Heavy Chain, Antibody Light Chain, Programmed cell death protein 1, ... (5 entities in total)
• Functional Keywords: pd-1 complex, immune checkpoint, inhibitor, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 62926.04

Authors

Liu, J.X.,Wang, G.Q. (deposition date: 2019-05-08, release date: 2019-12-11, Last modification date: 2024-11-20)

Primary citation

Liu, J.,Wang, G.,Liu, L.,Wu, R.,Wu, Y.,Fang, C.,Zhou, X.,Jiao, J.,Gu, Y.,Zhou, H.,Xie, Z.,Sun, Z.,Chen, D.,Dai, K.,Wang, D.,Tang, W.,Yang, T.T.C.
Study of the interactions of a novel monoclonal antibody, mAb059c, with the hPD-1 receptor.
Sci Rep, 9:17830-17830, 2019

PubMed Abstract: Programmed cell death 1 (PD-1) monoclonal antibodies have been approved by regulatory agencies for the treatment of various types of cancer, and the mechanism involves the restoration of T cell functions. We report herein the X-ray crystal structure of a fully human monoclonal antibody mAb059c fragment antigen-binding (Fab) in complex with the PD-1 extracellular domain (ECD) at a resolution of 1.70 Å. Structural analysis indicates 1) an epitope, comprising fragments from the C'D, BC and FG loops of PD-1, contributes to mAb059c interaction, 2) an unique conformation of the C'D loop and a different orientation of R86 enabling the capture of PD-1 by the antibody complementarity determining region (CDR) and the formation of one salt-bridge contact - ASP101(HCDR3):ARG86(PD-1), and 3) the contact of FG with light chain (LC) CDR3 is maintained by a second salt-bridge and two backbone hydrogen bonds. Interface analysis reveals that N-glycosylation sites 49, 74 and 116 on PD-1 do not contact mAb059c; while N58 in the BC loop is recognized by mAb059c heavy chain CDR1 and CDR2. Mutation of N58 attenuated mAb059c binding to PD-1. These findings and the novel anti-PD-1 antibody will facilitate better understanding of the mechanisms of the molecular recognition of PD-1 receptor by anti-PD-1 mAb and, thereby, enable the development of new therapeutics with an expanded spectrum of efficacy for unmet medical needs.

PubMed: 31780710
DOI: 10.1038/s41598-019-54231-w

Experimental method

X-RAY DIFFRACTION (1.7 Å)