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Regulation of Conformational Changes in C-reactive Protein Alters its Bioactivity

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Abstract

The acute phase C-reactive protein (CRP) is mainly synthesized and secreted by the liver in a cytokine-mediated response to infection or inflammation and circulates as a pentamer (pCRP) in plasma. Recent studies indicate that CRP is not only a marker but is directly involved in inflammation. CRP has a vital role in host defense and inflammation, metabolic function and scavenging through its ability for calcium depended binding to exogenous and endogenous molecules having phosphocholine followed by activation of the classical complement pathway. Accumulating evidence indicates that pCRP dissociates into monomeric CRP (mCRP) and most proinflammatory actions of CRP are only expressed following dissociation of its native pentameric assembly into mCRP. The dissociation of CRP into mCRP altogether promotes the ligand-binding capability. mCRP emerges to be the main conformation of CRP that participates in the regulation of local inflammation, however, little is identified concerning what triggers the significantly enhanced actions of mCRP and their binding to diverse ligands. The separation of mCRP from pCRP may be a direct relationship between CRP and inflammation. Here we review the current literature on CRP dissociation and its interaction with different ligands. The possibility to avoid the generation of the proinflammatory potential of mCRP has driven therapeutic approaches by targeting the dissociation mechanism of pCRP or inhibition of mCRP itself during inflammation.

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Abbreviations

CRP:

C-reactive protein

pCRP:

Petameric CRP

mCRP:

Monomeric CRP

CBS:

Cholesterol binding sequence

PC:

Phosphocholine

SAA:

Serum amyloid A

ECM:

Extracelluar matrix

NF-κB:

Nuclear factor kappa light chain enhancer of activated B cells

TNF alpha:

Tumour necrosis factor-alpha

STAT3:

Signal transducer and activator of transcription 3

LPS:

Lipopolysaccharide

LPC:

Lysophosphatidylcholine

ApoB:

Apolipoprotein B

LDL:

Low-density lipoprotein

C1q:

Complement component 1q

FIB:

Fibrinogen

Fn:

Fibronectin

VCAM-1:

Vascular-adhesion-molecule-1

ICAM-1:

Intercellular-adhesion-molecule-1

GPCR:

G protein-coupled receptor

EGFR:

Epidermal growth factor receptor

TCR:

T cell receptor

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Acknowledgements

We want to acknowledge the National Natural Science Foundation of China.

Funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC) project no (31870767).

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  1. MOE Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, 710061, China

    Naeem Ullah & Yi Wu

  2. Key Laboratory of Precision Medicine to Pediatric Diseases of Shaanxi Province, the Affiliated Children’s Hospital, Xi’an Jiaotong University, Xi’an, China

    Yi Wu

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Ullah, N., Wu, Y. Regulation of Conformational Changes in C-reactive Protein Alters its Bioactivity. Cell Biochem Biophys 80, 595–608 (2022). https://doi.org/10.1007/s12013-022-01089-x

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