Evidence map›Paper›PMID 27278931›Full record

ArticleScientific reports2016

Structure and function of chicken interleukin-1 beta mutants: uncoupling of receptor binding and in vivo biological activity.

Wen-Ting Chen, Wen-Yang Huang, Ting Chen, Emmanuel Oluwatobi Salawu, Dongli Wang, Yi-Zong Lee, Yuan-Yu Chang, Lee-Wei Yang, Shih-Che Sue, Xinquan Wang and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.3field-weighted citation impact, top 37% 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, 16 citations in OpenAlex.

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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

11 authors at 3 institutions in 2 countries.

Wen-Ting ChenInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Wen-Yang HuangInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Ting ChenInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Emmanuel Oluwatobi SalawuInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Dongli WangSchool of Life Science, Tsing Hua University, Beijing, China.
Yi-Zong LeeInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Yuan-Yu ChangInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Lee-Wei YangInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Shih-Che SueInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Xinquan WangSchool of Life Science, Tsing Hua University, Beijing, China.
Hsien-Sheng YinInstitute of Bioinformatics and Structural Biology, and College of Life Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
National Tsing Hua University · TWTsinghua University · CNAcademia Sinica · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Receptor-binding and subsequent signal-activation of interleukin-1 beta (IL-1β) are essential to immune and proinflammatory responses. We mutated 12 residues to identify sites important for biological activity and/or receptor binding. Four of these mutants with mutations in loop 9 (T117A, E118K, E118A, E118R) displayed significantly reduced biological activity. Neither T117A nor E118K mutants substantially affected receptor binding, whereas both mutants lack the IL-1β signaling in vitro but can antagonize wild-type (WT) IL-1β. Crystal structures of T117A, E118A, and E118K revealed that the secondary structure or surface charge of loop 9 is dramatically altered compared with that of wild-type chicken IL-1β. Molecular dynamics simulations of IL-1β bound to its receptor (IL-1RI) and receptor accessory protein (IL-1RAcP) revealed that loop 9 lies in a pocket that is formed at the IL-1RI/IL-1RAcP interface. This pocket is also observed in the human ternary structure. The conformations of above mutants in loop 9 may disrupt structural packing and therefore the stability in a chicken IL-1β/IL-1RI/IL-1RAcP signaling complex. We identify the hot spots in IL-1β that are essential to immune responses and elucidate a mechanism by which IL-1β activity can be inhibited. These findings should aid in the development of new therapeutics that neutralize IL-1 activity.

Indexed as

MutationAnimalsBinding SitesCell LineChickensCrystallography, X-RayGene Expression RegulationInterleukin-1betaInterleukin-1 Receptor Accessory ProteinModels, MolecularMolecular Dynamics SimulationProtein BindingProtein Structure, SecondaryReceptors, Interleukin-1Interleukin-1betaInterleukin-1 Receptor Accessory ProteinReceptors, Interleukin-1

Identifiers

PMID27278931
PMCPMC4899739
OpenAlexW2418394173

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.