Evidence map›Paper›PMID 29982679›Full record

ArticleGlycobiology2018

Biophysical analysis of sialic acid recognition by the complement regulator Factor H.

Christoph Q Schmidt, Agnes L Hipgrave Ederveen, Markus J Harder, Manfred Wuhrer, Thilo Stehle, Bärbel S Blaum

Open access · bronzeAbstract read
In one paragraph

Article in Glycobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 55 citations in OpenAlex.

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  11. Mechanisms by which Factor H protectsFrontiers in immunology · 2024
    Article
  12. Review
  13. Article
  14. Recent advances onSynthetic and systems biotechnology · 2023
    Review
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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

6 authors at 3 institutions in 2 countries.

Christoph Q SchmidtInstitute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Ulm, Germany.
Agnes L Hipgrave EderveenCenter for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef, Leiden, The Netherlands.
Markus J HarderInstitute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Ulm, Germany.
Manfred WuhrerCenter for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef, Leiden, The Netherlands.
Thilo StehleInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Bärbel S BlaumInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Leiden University Medical Center · NLUniversität Ulm · DEUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Complement factor H (FH), an elongated and substantially glycosylated 20-domain protein, is a soluble regulator of the complement alternative pathway (AP). It contains several glycan binding sites which mediate recognition of α2-3-linked sialic acid (FH domain 20) and glycosaminoglycans (domains 6-8 and 19-20). FH also binds the complement C3-activation product C3b, a powerful opsonin and focal point for the formation of C3-convertases of the AP feedback loop. In freely circulating FH the C3b binding site in domains 19-20 is occluded, a phenomenon that is not fully understood and could be mediated by an intramolecular interaction between FH's intrinsic sialylated glycosylation and its own sialic acid binding site. In order to assess this possibility, we characterized FH's sialylation with respect to glycosidic linkage type and searched for further potential, not yet characterized sialic acid binding sites in FH and its seven-domain spanning splice variant and fellow complement regulator FH like-1 (FHL-1). We also probed FH binding to the sialic acid variant Neu5Gc which is not expressed in humans but on heterologous erythrocytes that restrict the human AP and in FH transgenic mice. We find that FH contains mostly α2-6-linked sialic acid, making an intramolecular interaction with its α2-3-sialic acid specific binding site and an associated self-lock mechanism unlikely, substantiate that there is only a single sialic acid binding site in FH and none in FHL-1, and demonstrate direct binding of FH to the nonhuman sialic acid Neu5Gc, supporting the use of FH transgenic mouse models for studies of complement-related diseases.

Indexed as

AnimalsBinding SitesCarbohydrate ConformationComplement Factor HHumansMiceMice, TransgenicN-Acetylneuraminic AcidPolysaccharidesCFH protein, humanComplement Factor HN-Acetylneuraminic AcidPolysaccharides

Identifiers

PMID29982679
PMCPMC6142864
OpenAlexW2884428534

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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.