Sandbox Reserved 1121: Difference between revisions

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== Human C-reactive protein complexed with phosphocholine ==

Human C-Reactive Protein (CRP) is an acute phase protein belonging to the highly conserved pentraxin protein family <ref name="Thompson">PMID: 10368284</ref>. ~~Althought~~ it is a normal serum protein, its circulating concentration raises rapidly and extensively in a cytokine-mediated in response to an infection, an inflammation or a tissue injury. In this way, serum CRP rate is empirically dose to detect many human disease <ref name="Thompson"/>.

Human C-Reactive Protein (CRP) is an acute phase protein belonging to the highly conserved pentraxin protein family <ref name="Thompson">PMID: 10368284</ref>. Although it is a normal serum protein, its circulating concentration raises rapidly and extensively in a cytokine-mediated in response to an infection, an inflammation or a tissue injury. In this way, serum CRP rate is empirically dose to detect many human disease <ref name="Thompson"/>.

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== Structure ==

=== CRP structure ===

Primary structure:

The C-reactive protein is a homopentamer of non-covalently bound subunits. Each subunit is a 25 kDa protein consisting of 224 residues bound together <ref name="uniprot">[http://www.uniprot.org/uniprot/P02741 UniProtKB - P02741 (CRP_HUMAN)]</ref>.

Ser53, His95, Cys97, Asp112, Gly113, Gly136, Gly154, Val165, Leu166, Ile171, and Gly196 are the highly conserved residues in the primary sequence of CRP <ref name="kumar"/>.

Secondary structure:

The secondary structure is formed of one <scene name='71/719862/Helix/1'>α-helix</scene> and two antiparallel <scene name='71/719862/Sheet/1'>β-sheets</scene> <ref name="uniprot"/>. The predominant structure is β-sheet <ref>PMID: 1382589</ref> but short helical regions can be noticed for the residues 43 and 185 <ref name="kumar"/>. The residues Glu197 and Lys123 of CRP form an intermolecular ion pair <ref name="thompson">PMID: 10368284</ref>.

Tertiary and quaternary structure:

The structure of CRP has been determined by X-ray crystallograph at 3 Å resolution. Like SAP, the protein consists of five protomers, uncovalently bonded, arranged symmetrically around a central pore <ref name="Volanakis">PMID: 11532280</ref>.

~~Ser53, His95, Cys97, Asp112, Gly113, Gly136, Gly154, Val165, Leu166, Ile171, and Gly196 are the highly conserved residues in the primary sequence of CRP <ref name="kumar"/>.~~

The C-reactive protein is a homopentamer of non-covalently bound subunits. Each subunit is a 25 kDa protein consisting of 224 residues bound together. The secondary structure is formed of one <scene name='71/719862/Helix/1'>α-helix</scene> and two antiparallel <scene name='71/719862/Sheet/1'>β-sheets</scene> <ref>[http://www.uniprot.org/uniprot/P02741 UniProtKB - P02741 (CRP_HUMAN)]</ref>. The predominant structure is β-sheet <ref>PMID: 1382589</ref> but short helical regions can be noticed for the residues 43 and 185 <ref name="kumar"/>. The residues Glu197 and Lys123 of CRP form an intermolecular ion pair <ref name="thompson">PMID: 10368284</ref>.

The diameter of the CRP pentamer is 102 Å, the inner pore diameter is 30 Å and the diameter of a subunit is 36 Å <ref name="agrawal">PMID: 19799114 </ref>.

=== Ca2+ binding-site ===

CRP is a calcium dependent structure. ~~Effectively~~, Ca2+ is required for PC binding, and more precisely for the formation of the PC binding site thanks to structural rearrangements. The protection against denaturation and proteolysis is performed through Ca2+ binding too. In the absence of Ca2+, hCRP is cleaved between Asn145 and Phe146 by nagarse protease, and between Phe146 and Glu147 by pronase.

CRP is a calcium dependent structure. In fact, Ca2+ is required for PC binding, and more precisely for the formation of the PC binding site thanks to structural rearrangements. The protection against denaturation and proteolysis is performed through Ca2+ binding too. In the absence of Ca2+, hCRP is cleaved between Asn145 and Phe146 by nagarse protease, and between Phe146 and Glu147 by pronase.

Asp60, Asn61, Glu138, Asp140 and the main-chain carbonyl of Gln139 residues allow the first calcium ion binding, and the second is performed through Glu138, Asp140, Glu147 and Gln150 <ref name="ramadan">PMID: 12037301</ref>.

The two Ca2+-binding sites are overlapping in a loop. In the absence of Ca2+, the loop changes conformaion and releases the proteolysis site. Therefore Ca2+ protects CRP form proteolytic cleavage <ref name="agrawal"/>.

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@@ Line 2: / Line 2: @@
 == Human C-reactive protein complexed with phosphocholine ==
-Human C-Reactive Protein (CRP) is an acute phase protein belonging to the highly conserved pentraxin protein family <ref name="Thompson">PMID: 10368284</ref>. Althought it is a normal serum protein, its circulating concentration raises rapidly and extensively in a cytokine-mediated in response to an infection, an inflammation or a tissue injury. In this way, serum CRP rate is empirically dose to detect many human disease <ref name="Thompson"/>.
+Human C-Reactive Protein (CRP) is an acute phase protein belonging to the highly conserved pentraxin protein family <ref name="Thompson">PMID: 10368284</ref>. Although it is a normal serum protein, its circulating concentration raises rapidly and extensively in a cytokine-mediated in response to an infection, an inflammation or a tissue injury. In this way, serum CRP rate is empirically dose to detect many human disease <ref name="Thompson"/>.
@@ Line 9: / Line 9: @@
 == Structure ==
 === CRP structure ===
+Primary structure:
+The C-reactive protein is a homopentamer of non-covalently bound subunits. Each subunit is a 25 kDa protein consisting of 224 residues bound together <ref name="uniprot">[http://www.uniprot.org/uniprot/P02741 UniProtKB - P02741 (CRP_HUMAN)]</ref>.
+Ser53, His95, Cys97, Asp112, Gly113, Gly136, Gly154, Val165, Leu166, Ile171, and Gly196 are the highly conserved residues in the primary sequence of CRP <ref name="kumar"/>.
+Secondary structure:
+The secondary structure is formed of one <scene name='71/719862/Helix/1'>α-helix</scene> and two antiparallel <scene name='71/719862/Sheet/1'>β-sheets</scene> <ref name="uniprot"/>. The predominant structure is β-sheet <ref>PMID: 1382589</ref> but short helical regions can be noticed for the residues 43 and 185 <ref name="kumar"/>. The residues Glu197 and Lys123 of CRP form an intermolecular ion pair <ref name="thompson">PMID: 10368284</ref>.
+Tertiary and quaternary structure:
 The structure of CRP has been determined by X-ray crystallograph at 3 Å resolution. Like SAP, the protein consists of five protomers, uncovalently bonded, arranged symmetrically around a central pore <ref name="Volanakis">PMID: 11532280</ref>.
- Ser53, His95, Cys97, Asp112, Gly113, Gly136, Gly154, Val165, Leu166, Ile171, and Gly196 are the highly conserved residues in the primary sequence of CRP <ref name="kumar"/>.
-The C-reactive protein is a homopentamer of non-covalently bound subunits. Each subunit is a 25 kDa protein consisting of 224 residues bound together. The secondary structure is formed of one <scene name='71/719862/Helix/1'>α-helix</scene> and two antiparallel <scene name='71/719862/Sheet/1'>β-sheets</scene> <ref>[http://www.uniprot.org/uniprot/P02741 UniProtKB - P02741 (CRP_HUMAN)]</ref>. The predominant structure is β-sheet <ref>PMID: 1382589</ref> but short helical regions can be noticed for the residues 43 and 185 <ref name="kumar"/>. The residues Glu197 and Lys123 of CRP form an intermolecular ion pair <ref name="thompson">PMID: 10368284</ref>.
 The diameter of the CRP pentamer is 102 Å, the inner pore diameter is 30 Å and the diameter of a subunit is 36 Å <ref name="agrawal">PMID: 19799114 </ref>.
 === Ca<sup>2+</sup> binding-site ===
-CRP is a calcium dependent structure. Effectively, Ca<sup>2+</sup> is required for PC binding, and more precisely for the formation of the PC binding site thanks to structural rearrangements. The protection against denaturation and proteolysis is performed through Ca<sup>2+</sup> binding too. In the absence of Ca<sup>2+</sup>, hCRP is cleaved between Asn145 and Phe146 by nagarse protease, and between Phe146 and Glu147 by pronase.
+CRP is a calcium dependent structure. In fact, Ca<sup>2+</sup> is required for PC binding, and more precisely for the formation of the PC binding site thanks to structural rearrangements. The protection against denaturation and proteolysis is performed through Ca<sup>2+</sup> binding too. In the absence of Ca<sup>2+</sup>, hCRP is cleaved between Asn145 and Phe146 by nagarse protease, and between Phe146 and Glu147 by pronase.
 Asp60, Asn61, Glu138, Asp140 and the main-chain carbonyl of Gln139 residues allow the first calcium ion binding, and the second is performed through Glu138, Asp140, Glu147 and Gln150 <ref name="ramadan">PMID: 12037301</ref>.
 The two Ca<sup>2+</sup>-binding sites are overlapping in a loop. In the absence of Ca<sup>2+</sup>, the loop changes conformaion and releases the proteolysis site. Therefore Ca<sup>2+</sup> protects CRP form proteolytic cleavage <ref name="agrawal"/>.