Evidence map›Paper›PMID 32792612›Full record

ArticleScientific reports2020

Antibody-protein binding and conformational changes: identifying allosteric signalling pathways to engineer a better effector response.

Mohammed M Al Qaraghuli, Karina Kubiak-Ossowska, Valerie A Ferro, Paul A Mulheran

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.3field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 65 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

4 authors at 1 institution in 1 country.

Mohammed M Al QaraghuliDepartment of Chemical and Process Engineering, University of Strathclyde, Glasgow, G1 1XJ, UK. mohammed.al-qaraghuli@strath.ac.uk.
Karina Kubiak-OssowskaDepartment of Chemical and Process Engineering, University of Strathclyde, Glasgow, G1 1XJ, UK.
Valerie A FerroStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
Paul A MulheranDepartment of Chemical and Process Engineering, University of Strathclyde, Glasgow, G1 1XJ, UK.
University of Strathclyde · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Numerous monoclonal antibodies have been developed successfully for the treatment of various diseases. Nevertheless, the development of biotherapeutic antibodies is complex, expensive, and time-consuming, and to facilitate this process, careful structural analysis beyond the antibody binding site is required to develop a more efficacious antibody. In this work, we focused on protein antigens, since they induce the largest antibody changes, and provide interesting cases to compare and contrast. The structures of 15 anti-protein antibodies were analysed to compare the antigen-bound/unbound forms. Surprisingly, three different classes of binding-induced changes were identified. In class (B1), the antigen binding fragment distorted significantly, and we found changes in the loop region of the heavy chain's constant domain; this corresponds well with expected allosteric movements. In class (B2), we found changes in the same loop region without the overall distortion. In class (B3), these changes did not present, and only local changes at the complementarity determining regions were found. Consequently, structural analysis of antibodies is crucial for therapeutic development. Careful evaluation of allosteric movements must be undertaken to develop better effector responses, especially during the transformation of these antibodies from small fragments at the discovery stage to full antibodies at the subsequent development stages.

Indexed as

Allosteric SiteAnimalsAntibodiesAntigensBinding Sites, AntibodyCrystallography, X-RayHumansMiceModels, MolecularProtein BindingProtein ConformationAntibodiesAntigens

Identifiers

PMID32792612
PMCPMC7426963
OpenAlexW3046172755

What OpenQuestion holds

Textmetadata
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.