Evolution of C-Reactive Protein

Abstract

C-reactive protein (CRP) is an evolutionarily conserved protein. From arthropods to humans, CRP has been found in every organism where the presence of CRP has been sought. Human CRP is a pentamer made up of five identical subunits which binds to phosphocholine (PCh) in a Ca 2+ -dependent manner. In various species, we define a protein as CRP if it has any two of the following three characteristics: First, it is a cyclic oligomer of almost identical subunits of molecular weight 20–30 kDa. Second, it binds to PCh in a Ca 2+ -dependent manner. Third, it exhibits immunological cross-reactivity with human CRP. In the arthropod horseshoe crab, CRP is a constitutively expressed protein, while in humans, CRP is an acute phase plasma protein and a component of the acute phase response. As the nature of CRP gene expression evolved from a constitutively expressed protein in arthropods to an acute phase protein in humans, the definition of CRP became distinctive. In humans, CRP can be distinguished from other homologous proteins such as serum amyloid P, but this is not the case for most other vertebrates and invertebrates. Literature indicates that the binding ability of CRP to PCh is less relevant than its binding to other ligands. Human CRP displays structure-based ligand-binding specificities, but it is not known if that is true for invertebrate CRP. During evolution, changes in the intrachain disulfide and interchain disulfide bonds and changes in the glycosylation status of CRP may be responsible for different structure-function relationships of CRP in various species. More studies of invertebrate CRP are needed to understand the reasons behind such evolution of CRP. Also, CRP evolved as a component of and along with the development of the immune system. It is important to understand the biology of ancient CRP molecules because the knowledge could be useful for immunodeficient individuals.

How C-Reactive Protein Structural Isoforms With Distinctive Bioactivities Affect Disease Progression

“…As an evolutionarily conserved protein found in almost all lower species ( 18 ), it is tempting to speculate on the fundamental role that CRP may have in regulating innate defenses. Studies have appeared noting that CRP blood levels do increase in children with protein calorie malnutrition ( 19 – 21 ).…”

The Impact of Preoperative Inflammatory Markers on the Prognosis of Patients Undergoing Surgical Resection of Pulmonary Oligometastases

“…CRP is the prototypical acute phase protein in humans, produced by the liver in response to interleukin 6 (IL-6) and interleukin 1β (IL-1β), which are mainly released in inflammatory sites by immune and endothelial cells [ 21 ]. It is an evolutionary conserved protein, since it has been found in all the studied species, from arthropods to humans [ 22 ]. In humans, CRP mediates several mechanisms of host defense from bacterial infection through complement activation, regulation of phagocytosis, and the binding of various antigens on the cell membranes [ 21 ].…”

Functionality of C-Reactive Protein for Atheroprotection

“…Non-native CRP may serve as a tool to investigate the functions of CRP in every inflammatory disease involving deposition and aggregation of proteins, such as amyloidosis and autoimmune diseases (122). CRP may have been conserved throughout evolution for protection against disease and toxicity caused by protein misfolding and conformationally altered pathogenic proteins (123, 124).…”