Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	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.
Journal, issue, pages	Front Immunol, Vol. 12, Page 757633, Year 2021
Publish date	Dec 16, 2021
Authors	Dylan P Noone / Tijn T van der Velden / Thomas H Sharp /
PubMed 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 ...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 concentration lowered this pH-sensitivity for C1q, but not immunoglobulins, suggesting different modes of binding. These data suggest a model whereby a change in the ionic nature of CRP and immunological proteins can make it more adhesive to potential ligands without large structural rearrangements.
External links	Front Immunol / PubMed:34975846 / PubMed Central
Methods	EM (single particle)
Resolution	2.8 - 3.3 Å
Structure data	13456 7pk9 EMDB-13456, PDB-7pk9: C-reactive protein decamer at pH 7.5 Method: EM (single particle) / Resolution: 2.8 Å 13467 7pkb EMDB-13467, PDB-7pkb: C-reactive protein pentamer at pH 7.5 Method: EM (single particle) / Resolution: 3.2 Å 13468 7pkd EMDB-13468, PDB-7pkd: C-reactive protein decamer at pH 7.5 with phosphocholine ligand Method: EM (single particle) / Resolution: 3.3 Å 13469 7pke EMDB-13469, PDB-7pke: C-reactive protein pentamer at pH 7.5 with phosphocholine ligand Method: EM (single particle) / Resolution: 3.3 Å 13470 7pkf EMDB-13470, PDB-7pkf: C-reactive protein decamer at pH 5 Method: EM (single particle) / Resolution: 2.8 Å 13471 7pkg EMDB-13471, PDB-7pkg: C-reactive protein pentamer at pH 5 Method: EM (single particle) / Resolution: 3.3 Å 13472 7pkh EMDB-13472, PDB-7pkh: C-reactive protein decamer at pH 5 with phosphocholine ligand Method: EM (single particle) / Resolution: 3.0 Å
Chemicals	ChemComp-CA: Unknown entry ChemComp-HOH: WATER ChemComp-PC: PHOSPHOCHOLINE
Source	homo sapiens (human)
Keywords	IMMUNE SYSTEM / C-reactive protein / CRP / innate immunity