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Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1

2015; Elsevier BV; Volume: 23; Issue: 12 Linguagem: Inglês

10.1016/j.str.2015.09.010

1878-4186

Krzysztof M. Zak, Radosław Kitel, Sara Przetocka, Przemysław Golik, Katarzyna Guzik, Bogdan Musielak, Alexander Dömlingꝉ, Grzegorz Dubin, Tad A. Holak,

Immune Cell Function and Interaction

Summary Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has recently provided breakthrough progress in the treatment of melanoma, non-small cell lung cancer, and other types of cancer. Small-molecule drugs interfering with this pathway are highly awaited, but their development is hindered by insufficient structural information. This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex. First, it is shown that the ligand binding to human PD-1 is associated with significant plasticity within the receptor. Second, a detailed molecular map of the interaction surface is provided, allowing definition of the regions within both interacting partners that may likely be targeted by small molecules.