title: 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.
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland.
authors.forename: Krzysztof M
authors.initials: KM
authors.lastname: Zak
authors.affiliation: Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland; Department of Organic Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Kitel
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland.
authors.forename: Sara
authors.initials: S
authors.lastname: Przetocka
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Golik
authors.affiliation: Department of Organic Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Guzik
authors.affiliation: Department of Organic Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Musielak
authors.affiliation: Department for Drug Design, University of Groningen, A. Deusinglaan 9, 9713 AV Groningen, the Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dömling
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland. Electronic address: grzegorz.dubin@uj.edu.pl.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Dubin
authors.affiliation: Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland; Department of Organic Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland; Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. Electronic address: holak@chemia.uj.edu.pl.
authors.forename: Tad A
authors.initials: TA
authors.lastname: Holak
mesh_terms: D000595:Amino Acid Sequence; D060890:B7-H1 Antigen / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D008969:Molecular Sequence Data; D061026:Programmed Cell Death 1 Receptor / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor