Evidence map›Paper›PMID 42079264›Full record

ArticlebioRxiv : the preprint server for biology2026

Structure-Function Analysis of the FCRL5-IgG1 Fc Complex Reveals an Unappreciated Effect of Fc-Silent Antibodies on B cells.

Bart M Herpers, Mo Guo, Sanghwan Ko, George Delidakis, Jin Eyun Kim, Chang-Han Lee, Mohamed I Gadallah, Jennifer S Brodbelt, Y Jessie Zhang, George Georgiou

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Bart M HerpersDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Mo GuoDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
Sanghwan KoDepartment of Chemical Engineering, University of Texas at Austin, Austin, TX, USA.
George DelidakisDepartment of Chemical Engineering, University of Texas at Austin, Austin, TX, USA.
Jin Eyun KimDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Chang-Han LeeDepartment of Chemical Engineering, University of Texas at Austin, Austin, TX, USA.
Mohamed I GadallahDepartment of Chemistry, University of Texas at Austin, Austin, TX, USA.
Jennifer S BrodbeltDepartment of Chemistry, University of Texas at Austin, Austin, TX, USA.
Y Jessie ZhangDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
George GeorgiouDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.

Funding

Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological MoleculesR35GM139658 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BRODBELT, JENNIFER S. · 2021 to 2025
$2.9M
Systematic, molecular level analysis of the Fc receptor ligation on antibody effector functionsU01AI148118 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI GEORGIOU, GEORGE GEORGIOU, VARADARAJAN, NAVIN · 2020 to 2024
$2.3M
Deciphering the phosphorylation pattern of RNA polymerase II for eukaryotic transcriptionR35GM148356 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI Yan Jessie Zhang · 2023 to 2026
$2.3M
NIAID NIH HHS U01 AI148118NIGMS NIH HHS R35 GM139658NIGMS NIH HHS R35 GM148356
6 · The paper itself

Abstract

Human Fc receptor-like 5 (FCRL5) is a low-affinity IgG Fc receptor expressed on various B cell subsets and a potential therapeutic target. We discovered that commonly used Fc-silencing mutations, designed to prevent interactions between the Fcγ receptors on immune cells and the Fc domain of therapeutic IgG, do not prevent binding to FCRL5. As a result, unintended interactions between Fc-silent therapeutic IgG and human B cells may occur. We isolated a well-expressed variant of the Fc-binding portion of human FCRL5 by directed evolution and used structural modeling to guide the engineering of a human IgG1 Fc variant with approximately 100-fold higher affinity for FCRL5, enabling us to produce FCRL5:Fc complexes in solution. Native mass spectrometry, size exclusion chromatography, and the crystal structure of the FCRL5-IgG1 Fc complex solved at 3.4 Å indicate that the two proteins bind in a 1:1 stoichiometry. Furthermore, the structure revealed that FCRL5 binds to IgG1 Fc in a manner completely distinct from that of previously characterized Fc-binding proteins, such as Fcγ receptors, explaining why most Fc-silencing mutations do not disrupt FCRL5 binding. We demonstrate that selective cross-linking of FCRL5 with the B cell receptor (BCR)

Identifiers

PMID42079264
PMCPMC13131648

What Socratic 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 Socratic graph.