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= Human C-reactive protein (CRP) =

CRP binds to phosphocholine which is exposed on died or dying cells and expressed on the surfaces of pathogens. Then, it may activate the complement system via interaction with C1q, and enhance phagocytosis by macrophages via its binding to Fcγ receptors. In addition to the fact that this protein has been highly conserved during evolution, this suggests that CRP is a very important part of the innate immune response, in the host defense.

 

There are two <scene name='56/568019/Structure_of_crp_v2/1'>calcium-binding sites</scene> per CRP protomer.  

Consequently, there are a total of five ligands which bind the calcium ion in the first site, and four ligands in the second site.

Contrary to SAP (serum amyloid P) – an other protein of the pentraxin family – which has respectively 6 and 3 ligands in its two different calcium binding sites, both sites in CRP look like each other and have thus around the same affinity for the calcium ions.  

<Structure load='1b09' size='500' frame='true' align='left' caption='Insert caption here' scene='Insert optional scene name here' />

 

Phosphocholine is an universal phospholipid found particularly in the cell membranes and plasma lipoproteins of bacteria, fungi, plants and other eukaryotic organisms whose us, the human beings. However, CRP can only bind phosphocholine of our damaged or apoptotic cells, as head groups of phosphocholine are inaccessible to CRP in “normal” cells.  

- A hydrophobic pocket with the two key residues Phe66 and Glu81 located on the two extremities of the cavity. Phe66 interacts with the methyl group of the phosphocholine by hydrophobic interactions. Glu81 interacts with the positively charged choline nitrogen of the phosphocholine. The existence of this hydrophobic pocket (lined by Glu81, Gly79, Asn61 and Thr76) would allow bindings of phosphocholine analogues, maybe with higher affinity. This property is very interesting for the research of new drugs blocking the effects of CRP, sometimes harmful.

C1 is the first component of the classical pathway of the complement and consists of a complex of one C1q, two C1r, and two C1s molecules. C1q is the recognition subunit whereas C1r and C1s form the catalytic subunit. C1q is composed of three different polypeptide chains A, B and C and has a total molecular mass of 460Da. Each chain is present in four copies in the C1q molecule. C1q can bind different activator such as immunoglobulin (IgM and IgG) and CRP. In red, adjacent bound CRP molecules may present multiple binding sites via the A face for the C1q arms.

The bond of C1 to an activator, as CRP triggers the activation of the classical pathway of the complement. This pathway permits, inter alia, the lysis of infectious agent. An excessive activation of the classical pathway could induce tissue injury in ischemia. Thus, the use of inhibitors that attenuate the activation of the pathway by CRP could be a therapeutic approach in ischemia injury.  

Various studies have shown that CRP is able to bind to Fcγ receptor with an affinity comparable to that of IgG. These receptors expressed on hematopoietic cells are able to recognize the Fc portion of IgG. They induce phagocytosis in response to immune system attack. The interaction of CRP with Fcγ receptor suggests that CRP has an important role in the immune system and could explain that CRP concentration increases during the acute phase of the inflammation.