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

被引：430

作者：

Zak, Krzysztof M. ^{[1
,2
]}

Kitel, Radoslaw ^{[2
,3
]}

Przetocka, Sara ^{[1
,2
]}

Golik, Przemyslaw ^{[1
,2
]}

Guzik, Katarzyna ^{[3
]}

Musielak, Bogdan ^{[3
]}

Domling, Alexander ^{[4
]}

Dubin, Grzegorz ^{[1
,2
]}

Holak, Tad A. ^{[2
,3
,5
]}

机构：

[1] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, PL-30387 Krakow, Poland

[2] Jagiellonian Univ, Malopolska Ctr Biotechnol, PL-30387 Krakow, Poland

[3] Jagiellonian Univ, Dept Organ Chem, PL-30060 Krakow, Poland

[4] Univ Groningen, Dept Drug Design, NL-9713 AV Groningen, Netherlands

[5] Max Planck Inst Biochem, D-82152 Martinsried, Germany

来源：

STRUCTURE | 2015年 / 23卷 / 12期

关键词：

CD8; T-CELLS; ANTI-PD-L1; ANTIBODY; CRYSTAL-STRUCTURE; BLOCKADE; INHIBITORS; MPDL3280A; RESPONSES; BLADDER; DESIGN; SAFETY;

D O I：

10.1016/j.str.2015.09.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2341 / 2348

页数：8

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