Sandbox Reserved 1121: Difference between revisions

The five protomers are related one with an other by three salt bridges that mainly involve the 115-123 loop of one protomer and the 40-42 and 197-202 regions of the other promoter <ref name="Volanakis"/>.

[[Image:Loop Ca2+.PNG | thumb | Loop involved in Ca²⁺-binding site (left), Ca²⁺-depleted structure (right) <ref name="PyMol">The PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC.</ref>]]

CRP is a calcium dependent structure. The face B binds two Ca²⁺ ions per subunit. The ligands are bound asymmetrically in both Ca²⁺-binding sites. The residues of the site 1 include Asp60, Asn61, Glu138, Asp140, the carbonyl oxygen of the residue 139 and one oxygen of Asp60. The site 1 provides a total of five ligands for the Ca²⁺ ion. The site 2 residues include Gln138, Asp140, Gln150 and non-coordinating Glu147. The site 2 provides four ligands for the Ca²⁺ ion. The two Ca²⁺-binding sites are of equal affinity for Ca²⁺ and are only differentiated by the carbonyl oxygen ligand. In presence of Ca²⁺, the two Ca²⁺-binding sites are overlapping in a loop. When the Ca²⁺ sites are free, the residues 140 to 150 form a loop away from the molecule<ref name="Thompson"/>. This releases the proteolysis site <ref name="agrawal"/>, which induces the cleavage of CRP between Asn145 and Phe146 by nagarase protease and between Phe146 and Glu147 by pronase <ref name="ramadan">PMID: 12037301</ref>. Therefore Ca²⁺ protects CRP form proteolytic cleavage and from degradation <ref name="agrawal"/>.

[[Image:Phosphocholine.PNG | thumb | PC and Ca²⁺-binding site <ref name="PyMol"/>]]

Phosphocholine (PC) is a phospholipid found in cell membranes and a plasma lipoprotein <ref name="Thompson"/>. The PC-binding site is a hydrophobic pocket constituted by the residues Leu64, Phe66, Thr76 and the two Ca²⁺ <ref name="agrawal"/><ref name="Volanakis"/>. This residues are very important because if one of them is mutated into an other, the avidity is significantly reduced <ref name="Volanakis"/>.

Two of the oxygens of the phosphate group directly co-ordinate with the two Ca²⁺ bound on the CRP <ref name="Volanakis"/>, leaving the third oxygen pointing away from the binding sites <ref name="Thompson"/>.The choline group rests within the hydrophobic pocket.  

The three choline methyl groups makes hydrophobic interactions with the exposed face of Phe66, while, the positively charged quartenary choline nitrogen interacts with the side of Glu81 which is located on the other side of the pocket <ref name="Volanakis"/>.

The choline function of PC interacts with the two key residues Phe66 and Glu81, therefore PC lies inside the PC-binding site <ref name="kumar"/> <ref name="agrawal"/>.

The affinity of CRP for PC increases when the concentration of PC does so. A surface containing a high density of PC, such as C-polycaccharide, is therefore propitious to the CRP-binding <ref name="duclos"/>.

CRP can also bind chromatin, histones, small nuclear ribonucleoproteins nuclear envelop proteins and nucleosomes Ca²⁺-dependently <ref name="agrawal"/>.