Sandbox Reserved 821: Difference between revisions

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== '''The Calcium and Phosphocholine binding sites''' ==

==='''''Calcium'''''===

There are two calcium-binding sites per CRP protomer.

One is consisting of residues Asp60, Asn61, Glu138, Asp140 and the mainchain carbonyl oxygen of residue 139 of the CRP.

The other contains residues Gln138, Asp140, Gln150 and Glu147 of the CRP.

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.

Mainly, CRP contains either no calcium bound, or the two calcium bound in its both sites.

In the first case, residues of CRP protomers – of which Asp140 and Gln150 which are a part of the calcium binding sites – form a loop far away of the body of the protein, allowing a proteolysis site previously hidden to be exposed.

In the other case, the calcium ions (separated by 4Å) are a part of the binding sites of other molecules, such as phosphocholine.

==='''''Phosphocholine'''''===

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.

Different sites of the CRP are needed to bind phosphocholine:

- 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.

- The two bound calcium ions which interact with the phosphate group of the phosphocholine (two oxygen of the phosphate group).

The role of CRP to protect the host of infection and inflammation is thus certainly done first by binding to phosphocholine or other ligands such as phosphoethanolamine, and then by activation of the classical complement pathway via interaction with C1q or phagocytosis via interaction with Fc receptors.

== '''Interaction with C1q''' ==

== '''Interaction with Fcγ receptors''' ==

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@@ Line 20: / Line 20: @@
 == '''The Calcium and Phosphocholine binding sites''' ==
+==='''''Calcium'''''===
+There are two calcium-binding sites per CRP protomer.
+One is consisting of residues Asp60, Asn61, Glu138, Asp140 and the mainchain carbonyl oxygen of residue 139 of the CRP.
+The other contains residues Gln138, Asp140, Gln150 and Glu147 of the CRP.
+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.
+Mainly, CRP contains either no calcium bound, or the two calcium bound in its both sites.
+In the first case, residues of CRP protomers – of which Asp140 and Gln150 which are a part of the calcium binding sites – form a loop far away of the body of the protein, allowing a proteolysis site previously hidden to be exposed.
+In the other case, the calcium ions (separated by 4Å) are a part of the binding sites of other molecules, such as phosphocholine.
+==='''''Phosphocholine'''''===
+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.
+Different sites of the CRP are needed to bind phosphocholine:
+- 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.
+- The two bound calcium ions which interact with the phosphate group of the phosphocholine (two oxygen of the phosphate group).
+The role of CRP to protect the host of infection and inflammation is thus certainly done first by binding to phosphocholine or other ligands such as phosphoethanolamine, and then by activation of the classical complement pathway via interaction with C1q or phagocytosis via interaction with Fc receptors.
 == '''Interaction with C1q''' ==
 == '''Interaction with Fcγ receptors''' ==