Evidence map›Paper›PMID 23853097›Full record

ArticleThe Journal of biological chemistry2013

Structural insights into the neutralization mechanism of monoclonal antibody 6C2 against ricin.

Yuwei Zhu, Jianxin Dai, Tiancheng Zhang, Xu Li, Pengfei Fang, Huajing Wang, Yongliang Jiang, Xiaojie Yu, Tian Xia, Liwen Niu and 2 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.2field-weighted citation impact, top 23% of its field
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

7 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Yuwei ZhuFrom the Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China,; the Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, China.
Jianxin Daithe International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China, and; the State Key Laboratory of Antibody Medicine and Targeting Therapy, Shanghai 201203, China.
Tiancheng Zhangthe International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China, and; the State Key Laboratory of Antibody Medicine and Targeting Therapy, Shanghai 201203, China.
Xu LiFrom the Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China,; the Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, China.
Pengfei FangFrom the Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China,; the Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, China.
Huajing Wangthe International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China, and; the State Key Laboratory of Antibody Medicine and Targeting Therapy, Shanghai 201203, China.
Yongliang JiangFrom the Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China,; the Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, China.
Xiaojie Yuthe International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China, and; the State Key Laboratory of Antibody Medicine and Targeting Therapy, Shanghai 201203, China.
Tian Xiathe International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China, and; the State Key Laboratory of Antibody Medicine and Targeting Therapy, Shanghai 201203, China.
Liwen NiuFrom the Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China,; the Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, China.
Yajun Guothe International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China, and; the State Key Laboratory of Antibody Medicine and Targeting Therapy, Shanghai 201203, China. Electronic address: yjguo@smmu.edu.cn.
Maikun TengFrom the Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China,; the Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, China,. Electronic address: mkteng@ustc.edu.cn.
Second Military Medical University · CNChinese Academy of Sciences · CNUniversity of Science and Technology of China · CNHefei National Center for Physical Sciences at Nanoscale · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ricin belongs to the type II ribosome-inactivating proteins that depurinate the universally conserved α-sarcin loop of rRNA. The RNA N-glycosidase activity of ricin also largely depends on the ribosomal proteins that play an important role during the process of rRNA depurination. Therefore, the study of the interaction between ricin and the ribosomal elements will be better to understand the catalysis mechanism of ricin. The antibody 6C2 is a mouse monoclonal antibody exhibiting unusually potent neutralizing ability against ricin, but the neutralization mechanism remains unknown. Here, we report the 2.8 Å crystal structure of 6C2 Fab in complex with the A-chain of ricin (RTA), which reveals an extensive antigen-antibody interface that contains both hydrogen bonds and van der Waals contacts. The complementarity-determining region loops H1, H2, H3, and L3 form a pocket to accommodate the epitope on the RTA (residues Asp(96)-Thr(116)). ELISA results show that Gln(98), Glu(99), Glu(102), and Thr(105) (RTA) are the key residues that play an important role in recognizing 6C2. With the perturbation of the 6C2 Fab-RTA interface, 6C2 loses its neutralization ability, measured based on the inhibition of protein synthesis in a cell-free system. Finally, we propose that the neutralization mechanism of 6C2 against ricin is that the binding of 6C2 hinders the interaction between RTA and the ribosome and the surface plasmon resonance and pulldown results confirm our hypothesis. In short, our data explain the neutralization mechanism of mAb 6C2 against ricin and provide a structural basis for the development of improved antibody drugs with better specificity and higher affinity.

Indexed as

AnimalsAntibodies, Monoclonal, Murine-DerivedAntibodies, NeutralizingBinding Sites, AntibodyComplementarity Determining RegionsMiceProtein Structure, QuaternaryProtein Structure, SecondaryRicinAntibodies, Monoclonal, Murine-DerivedAntibodies, NeutralizingComplementarity Determining RegionsRicinAntibodiesRibosomal RNA ProcessingRibosomesRIPStructural Biology

Identifiers

PMID23853097
PMCPMC3757180
OpenAlexW2008328260

What OpenQuestion holds

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Registered trials

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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.