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[[Image:Image2.jpg|300px|right|thumb| CRP structure]] | [[Image:Image2.jpg|300px|right|thumb| CRP structure]] | ||
==CRP, C-reactive Protein== | ==CRP, C-reactive Protein== | ||
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:There is individual variability in baseline CRP, resulting from non-genetic or genetic factors. Indeed, a polymorphism in the CRP gene intron and promoter has been described, that pertubs expression level. | :There is individual variability in baseline CRP, resulting from non-genetic or genetic factors. Indeed, a polymorphism in the CRP gene intron and promoter has been described, that pertubs expression level. | ||
The intron of the gene of the CRP is formed by 278 nucleotides, containing a segment of 39 nucleotides rich in GT bases. This segment could be responsible for the training of the left-handed helix of the Z-form DNA of the CRP. The individuals possessing a particular allele combination have a lower concentration of the CRP. It is probably due to structural modifications of the DNA which would affect the transcription of the gene. | :The intron of the gene of the CRP is formed by 278 nucleotides, containing a segment of 39 nucleotides rich in GT bases. This segment could be responsible for the training of the left-handed helix of the Z-form DNA of the CRP. The individuals possessing a particular allele combination have a lower concentration of the CRP. It is probably due to structural modifications of the DNA which would affect the transcription of the gene. | ||
:Within the promoter, several polymorphisms were discovered in transcription factor binding E-box sites, what seem to significantly influence the rate of the CRP into the blood. | :Within the promoter, several polymorphisms were discovered in transcription factor binding E-box sites, what seem to significantly influence the rate of the CRP into the blood. | ||
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:In the presence of calcium, CRP is specifically bound in phosphocholine residues. We find phosphocholine in the microbial polysaccharides. | :In the presence of calcium, CRP is specifically bound in 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. | :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. | :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. | :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. | ||
Two binding sites of equal affinity to calcium exist on the recognition face 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. | Two binding sites of equal affinity to calcium exist on the recognition face 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. | ||
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:The CRP also binds to receptors of IgG, such as FcgRI and FcgRII, 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. | :The CRP also binds to receptors of IgG, such as FcgRI and FcgRII, 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. | ||
==About this Structure== | |||
1PTH is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. The May 2001 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb17_1.html Molecule of the Month]by David S. Goodsell features ''Cyclooxygenase''. [http://dx.doi.org/10.2210/rcsb_pdb/mom_2001_510.2210/rcsb_pdb/mom_2001_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PTH OCA]. | |||
==References== | |||
<<references/> | |||
[[Category: Cyclooxygenase]] | |||
[[Category: Prostaglandin-endoperoxide synthase]] | |||
[[Category: Dioxygenase]] | |||
[[Category: Peroxidase]] | |||
