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.
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.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- C-reactive protein is a broad-spectrum capsule-binding receptor for hepatic capture of blood-borne bacteria.The EMBO journal · 2025Article
- Overcoming Preferred Orientation in Cryo-EM With Ultrasonic Excitation During Vitrification.bioRxiv : the preprint server for biology · 2025Article
- Redefining CRP in tissue injury and repair: more than an acute pro-inflammatory mediator.Frontiers in immunology · 2025Review
- 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 · 2024Article
- Lifting the Concentration Limit of Mass Photometry by PEG Nanopatterning.Nano letters · 2024Article
- Selection and characterization of a peptide-based complement modulator targeting C1 of the innate immune system.RSC chemical biology · 2024Article
- Factors affecting macromolecule orientations in thin films formed in cryo-EM.Acta crystallographica. Section D, Structural biology · 2024Article
- An evolutionarily conserved function of C-reactive protein is to prevent the formation of amyloid fibrils.Frontiers in immunology · 2024Article
- C-reactive protein: structure, function, regulation, and role in clinical diseases.Frontiers in immunology · 2024Review
- Structurally Altered, Not Wild-Type, Pentameric C-Reactive Protein Inhibits Formation of Amyloid-β Fibrils.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- PTX3 structure determination using a hybrid cryoelectron microscopy and AlphaFold approach offers insights into ligand binding and complement activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Editorial: Interactions of Pentraxins and Complement in Infection, Inflammation, and Cancer.Frontiers in immunology · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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
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