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


ABSTRACT: 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.

SUBMITTER: Zak KM 

PROVIDER: S-EPMC4752817 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Zak Krzysztof M KM   Kitel Radoslaw R   Przetocka Sara S   Golik Przemyslaw P   Guzik Katarzyna K   Musielak Bogdan B   Dömling Alexander A   Dubin Grzegorz G   Holak Tad A TA  

Structure (London, England : 1993) 20151022 12


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 li  ...[more]

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