|
|
| Line 55: |
Line 55: |
|
| |
|
| :This variability should be taken into account when using the CRP as a predictive biomarker. [http://www.rndsystems.com/cb_detail_objectname_SU05_CReactiveProtein.aspx <5>] | | :This variability should be taken into account when using the CRP as a predictive biomarker. [http://www.rndsystems.com/cb_detail_objectname_SU05_CReactiveProtein.aspx <5>] |
|
| |
| ==Ligand==
| |
|
| |
| <Structure load='1b09' size='250' frame='true' align='right' caption='CRP complexed with Phosphocholine' scene='Insert optional scene name here' />
| |
|
| |
| :In the presence of calcium, CRP is '''specifically''' bound to phosphocholine residues. We find phosphocholine in the microbial polysaccharides.
| |
| :The wide distribution of phosphocholine in polysaccharides of pathogenic and in cellular membranes allows CRP to recognize a range of pathogenic targets as well as the damaged membranes and necrosed cells of the host. The ligand, the phosphocholine, does not appear normally on the surface of cells, but '''is exposed by cellular damages caused by phospholipases'''.
| |
| :After this connection, CRP activates the '''classical complement pathway''' in the absence of antibody, and '''opsonizes ligands''', with the aim of their phagocytosis.
| |
| :Indeed, when CRP is bound in the ligand, it is recognized by the factor CIq, what activates powerfully the classical complement pathway, committing the factor C3. There is then formation of the membrane attack complex C5-C9 on the surface of the ligand, what entails its phagocytosis.
| |
| [http://www.ncbi.nlm.nih.gov/pubmed/11532280 <6>]
| |
|
| |
| :On the recognition face, there are two binding sites of equal affinity to calcium, consisting of residues '''Asp60, Asn61, Glu138, Asp140, and the main chain carbonyl of Gln139''' for the first calcium ion and residues '''Glu138, Asp140, Gln150, and Glu147''' for the second calcium ion. It appears an interaction between the two calcium ions and the oxygens of the phosphate group and the choline group, which rests in a hydrophobic pocket formed by residues Phe66, Leu64, Thr76, and Glu81. The face of Phe66 is exposed, allowing it to have hydrophobic interactions with the methyl groups of the choline. Glu81 interacts with the positively charged nitrogen on choline.
| |
| :The binding site for Clq is found of the effector phase, or opposite side the phosphocholine binding site. This site is located at the open shallow end of a cleft, where a depression is formed. The boundaries of the pocket are formed by the loops 86-92 and 112-114 on the protomer's C-terminus, and Tyr175 on the other. Residues Asp112 and Tyr75 are the contact residues for the Clq. The substitution of these residues with Ala results in significantly reduced affinity for CRP. Glu88 causes a conformational changed in CRP which is needed before complementation activation can occur, whereas Asn158and His38 are needed for the proper geometry at the binding site. Substitution of Ala for Lys114 resulted in more Clq-binding and increased complement activation.
| |
| [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>]
| |
|
| |
|
| |
| :The CRP also binds to receptors of IgG, the FcγR, present on the surface of phagocytic cells. She acts as an opsonin. But we do not still know the exact location of the binding sites of these molecules.
| |
| [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/<2>]
| |
|
| |
|
|
| |
|
