Evidence map›Paper›PMID 34975846›Full record

ArticleFrontiers in immunology2021

Cryo-Electron Microscopy and Biochemical Analysis Offer Insights Into the Effects of Acidic pH, Such as Occur During Acidosis, on the Complement Binding Properties of C-Reactive Protein.

Dylan P Noone, Tijn T van der Velden, Thomas H Sharp

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Structural basis for surface activation of the classical complement cascade by the short pentraxin C-reactive protein.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Article
  6. Article
  7. Factors affecting macromolecule orientations in thin films formed in cryo-EM.Acta crystallographica. Section D, Structural biology · 2024
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
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

3 authors at 1 institution in 1 country.

Dylan P NooneDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Tijn T van der VeldenDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Thomas H SharpDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Leiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The pentraxin family of proteins includes C-reactive protein (CRP), a canonical marker for the acute phase inflammatory response. As compared to normal physiological conditions in human serum, under conditions associated with damage and inflammation, such as acidosis and the oxidative burst, CRP exhibits modulated biochemical properties that may have a structural basis. Here, we explore how pH and ligand binding affect the structure and biochemical properties of CRP. Cryo-electron microscopy was used to solve structures of CRP at pH 7.5 or pH 5 and in the presence or absence of the ligand phosphocholine (PCh), which yielded 7 new high-resolution structures of CRP, including pentameric and decameric complexes. Structures previously derived from crystallography were imperfect pentagons, as shown by the variable angles between each subunit, whereas pentameric CRP derived from cryoEM was found to have C5 symmetry, with subunits forming a regular pentagon with equal angles. This discrepancy indicates flexibility at the interfaces of monomers that may relate to activation of the complement system by the C1 complex. CRP also appears to readily decamerise in solution into dimers of pentamers, which obscures the postulated binding sites for C1. Subtle structural rearrangements were observed between the conditions tested, including a putative change in histidine protonation that may prime the disulphide bridges for reduction and enhanced ability to activate the immune system. Enzyme-linked immunosorbent assays showed that CRP had markedly increased association to the C1 complex and immunoglobulins under conditions associated with acidosis, whilst a reduction in the Ca

Indexed as

AcidosisCalciumComplement System ProteinsConserved SequenceC-Reactive ProteinCryoelectron MicroscopyHumansHydrogen-Ion ConcentrationInflammationModels, MolecularProtein BindingProtein ConformationProtein MultimerizationSequence AlignmentStructure-Activity RelationshipCalciumComplement System ProteinsC-Reactive ProteinacidosiscomplementCRPcryoEMELISAstructural biology

Identifiers

PMID34975846
PMCPMC8716467
OpenAlexW4200518624

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.