Evidence map›Paper›PMID 28165004›Full record

ArticleNature communications2017

An unexpected N-terminal loop in PD-1 dominates binding by nivolumab.

Shuguang Tan, Hao Zhang, Yan Chai, Hao Song, Zhou Tong, Qihui Wang, Jianxun Qi, Gary Wong, Xiaodong Zhu, William J Liu and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

144 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Non-Clinical Evaluation of the Anti-PD-1 Antibody UDIZ-007.Pharmaceuticals (Basel, Switzerland) · 2026
    Article
  6. A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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84 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Shuguang TanCAS Key Laboratory of Microbial Physiological and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Hao ZhangCAS Key Laboratory of Microbial Physiological and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Yan ChaiCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Hao SongResearch Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
Zhou TongCAS Key Laboratory of Microbial Physiological and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Qihui WangCAS Key Laboratory of Microbial Physiological and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Jianxun QiCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Gary WongCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Xiaodong ZhuBeijing Combio Co., Ltd., Beijing 100111, China.
William J LiuNational Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
Shan GaoCAS Key Laboratory of Bio-medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
Zhongfu WangKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education and Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an 710069, China.
Yi ShiCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Fuquan YangLaboratory of Protein and Peptide Pharmaceuticals &Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
George F GaoCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Jinghua YanCAS Key Laboratory of Microbial Physiological and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer immunotherapy by targeting of immune checkpoint molecules has been a research 'hot-spot' in recent years. Nivolumab, a human monoclonal antibody targeting PD-1, has been widely used clinically since 2014. However, the binding mechanism of nivolumab to PD-1 has not yet been shown, despite a recent report describing the complex structure of pembrolizumab/PD-1. It has previously been speculated that PD-1 glycosylation is involved in nivolumab recognition. Here we report the complex structure of nivolumab with PD-1 and evaluate the effects of PD-1 N-glycosylation on the interactions with nivolumab. Structural and functional analyses unexpectedly reveal an N-terminal loop outside the IgV domain of PD-1. This loop is not involved in recognition of PD-L1 but dominates binding to nivolumab, whereas N-glycosylation is not involved in binding at all. Nivolumab binds to a completely different area than pembrolizumab. These results provide the basis for the design of future inhibitory molecules targeting PD-1.

Indexed as

Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenCrystallography, X-RayDrug DesignGlycosylationHumansImmunotherapyNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorProtein BindingProtein DomainsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenCD274 protein, humanNivolumabPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptor

Identifiers

PMID28165004
PMCPMC5303876

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.