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Relevance of lipoproteins, membranes, and extracellular vesicles in understanding C-reactive protein biochemical structure and biological activities

Early purification protocols for C-reactive protein (CRP) often involved co-isolation of lipoproteins, primarily very low-density lipoproteins (VLDLs). The interaction with lipid particles was initially attributed to CRP’s calcium-dependent binding affinity for its primary ligand—phosphocholine—the...

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Autores principales: Potempa, Lawrence A., Qiu, Wei Qiao, Stefanski, Ashley, Rajab, Ibraheem M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493015/
https://www.ncbi.nlm.nih.gov/pubmed/36158829
http://dx.doi.org/10.3389/fcvm.2022.979461
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author Potempa, Lawrence A.
Qiu, Wei Qiao
Stefanski, Ashley
Rajab, Ibraheem M.
author_facet Potempa, Lawrence A.
Qiu, Wei Qiao
Stefanski, Ashley
Rajab, Ibraheem M.
author_sort Potempa, Lawrence A.
collection PubMed
description Early purification protocols for C-reactive protein (CRP) often involved co-isolation of lipoproteins, primarily very low-density lipoproteins (VLDLs). The interaction with lipid particles was initially attributed to CRP’s calcium-dependent binding affinity for its primary ligand—phosphocholine—the predominant hydrophilic head group expressed on phospholipids of most lipoprotein particles. Later, CRP was shown to additionally express binding affinity for apolipoprotein B (apo B), a predominant apolipoprotein of both VLDL and LDL particles. Apo B interaction with CRP was shown to be mediated by a cationic peptide sequence in apo B. Optimal apo B binding required CRP to be surface immobilized or aggregated, treatments now known to structurally change CRP from its serum soluble pentamer isoform (i.e., pCRP) into its poorly soluble, modified, monomeric isoform (i.e., mCRP). Other cationic ligands have been described for CRP which affect complement activation, histone bioactivities, and interactions with membranes. mCRP, but not pCRP, binds cholesterol and activates signaling pathways that activate pro-inflammatory bioactivities long associated with CRP as a biomarker. Hence, a key step to express CRP’s biofunctions is its conversion into its mCRP isoform. Conversion occurs when (1) pCRP binds to a membrane surface expressed ligand (often phosphocholine); (2) biochemical forces associated with binding cause relaxation/partial dissociation of secondary and tertiary structures into a swollen membrane bound intermediate (described as mCRP(m) or pCRP*); (3) further structural relaxation which leads to total, irreversible dissociation of the pentamer into mCRP and expression of a cholesterol/multi-ligand binding sequence that extends into the subunit core; (4) reduction of the CRP subunit intrachain disulfide bond which enhances CRP’s binding accessibility for various ligands and activates acute phase proinflammatory responses. Taken together, the biofunctions of CRP involve both lipid and protein interactions and a conformational rearrangement of higher order structure that affects its role as a mediator of inflammatory responses.
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spelling pubmed-94930152022-09-23 Relevance of lipoproteins, membranes, and extracellular vesicles in understanding C-reactive protein biochemical structure and biological activities Potempa, Lawrence A. Qiu, Wei Qiao Stefanski, Ashley Rajab, Ibraheem M. Front Cardiovasc Med Cardiovascular Medicine Early purification protocols for C-reactive protein (CRP) often involved co-isolation of lipoproteins, primarily very low-density lipoproteins (VLDLs). The interaction with lipid particles was initially attributed to CRP’s calcium-dependent binding affinity for its primary ligand—phosphocholine—the predominant hydrophilic head group expressed on phospholipids of most lipoprotein particles. Later, CRP was shown to additionally express binding affinity for apolipoprotein B (apo B), a predominant apolipoprotein of both VLDL and LDL particles. Apo B interaction with CRP was shown to be mediated by a cationic peptide sequence in apo B. Optimal apo B binding required CRP to be surface immobilized or aggregated, treatments now known to structurally change CRP from its serum soluble pentamer isoform (i.e., pCRP) into its poorly soluble, modified, monomeric isoform (i.e., mCRP). Other cationic ligands have been described for CRP which affect complement activation, histone bioactivities, and interactions with membranes. mCRP, but not pCRP, binds cholesterol and activates signaling pathways that activate pro-inflammatory bioactivities long associated with CRP as a biomarker. Hence, a key step to express CRP’s biofunctions is its conversion into its mCRP isoform. Conversion occurs when (1) pCRP binds to a membrane surface expressed ligand (often phosphocholine); (2) biochemical forces associated with binding cause relaxation/partial dissociation of secondary and tertiary structures into a swollen membrane bound intermediate (described as mCRP(m) or pCRP*); (3) further structural relaxation which leads to total, irreversible dissociation of the pentamer into mCRP and expression of a cholesterol/multi-ligand binding sequence that extends into the subunit core; (4) reduction of the CRP subunit intrachain disulfide bond which enhances CRP’s binding accessibility for various ligands and activates acute phase proinflammatory responses. Taken together, the biofunctions of CRP involve both lipid and protein interactions and a conformational rearrangement of higher order structure that affects its role as a mediator of inflammatory responses. Frontiers Media S.A. 2022-09-08 /pmc/articles/PMC9493015/ /pubmed/36158829 http://dx.doi.org/10.3389/fcvm.2022.979461 Text en Copyright © 2022 Potempa, Qiu, Stefanski and Rajab. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Potempa, Lawrence A.
Qiu, Wei Qiao
Stefanski, Ashley
Rajab, Ibraheem M.
Relevance of lipoproteins, membranes, and extracellular vesicles in understanding C-reactive protein biochemical structure and biological activities
title Relevance of lipoproteins, membranes, and extracellular vesicles in understanding C-reactive protein biochemical structure and biological activities
title_full Relevance of lipoproteins, membranes, and extracellular vesicles in understanding C-reactive protein biochemical structure and biological activities
title_fullStr Relevance of lipoproteins, membranes, and extracellular vesicles in understanding C-reactive protein biochemical structure and biological activities
title_full_unstemmed Relevance of lipoproteins, membranes, and extracellular vesicles in understanding C-reactive protein biochemical structure and biological activities
title_short Relevance of lipoproteins, membranes, and extracellular vesicles in understanding C-reactive protein biochemical structure and biological activities
title_sort relevance of lipoproteins, membranes, and extracellular vesicles in understanding c-reactive protein biochemical structure and biological activities
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493015/
https://www.ncbi.nlm.nih.gov/pubmed/36158829
http://dx.doi.org/10.3389/fcvm.2022.979461
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