Sandbox Reserved 1121
From Proteopedia
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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"/> | 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 Da protein consisting of 224 residues bound together. The secondary structure is formed of four α-helices and three antiparallel β-sheets (five-stranded, three-stranded and seven-stranded).<ref>http://www.uniprot.org/uniprot/P02741</ref> The predominant structure is β-sheet <ref>http://www.unco.edu/nhs/Chemistry/faculty/dong/pub/pentraxin.pdf</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" /> | The C-reactive protein is a homopentamer of non-covalently bound subunits. Each subunit is a 25 Da protein consisting of 224 residues bound together. The secondary structure is formed of four α-helices and three antiparallel β-sheets (five-stranded, three-stranded and seven-stranded).<ref>http://www.uniprot.org/uniprot/P02741</ref> The predominant structure is β-sheet <ref>http://www.unco.edu/nhs/Chemistry/faculty/dong/pub/pentraxin.pdf</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" /> | ||
| - | The diameterof the CRP pentamer is 102 Å, the inner pore diameter is 30 Å and the diameter of a subunit is 36 Å. <ref>A. Agrawal, P. P. Singh, B. Bottazzi, C. Garlanda, A. Mantovani, Pattern recognition by Pentraxins, Adv Exp Med Biol. 2009; 653: 98-116</ref> | + | The diameterof 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">A. Agrawal, P. P. Singh, B. Bottazzi, C. Garlanda, A. Mantovani, Pattern recognition by Pentraxins, Adv Exp Med Biol. 2009; 653: 98-116</ref> |
=== Ca<sup>2+</sup> binding-site === | === 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. 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. | ||
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">Ramadan, M. A. M., Shrive, A. K., Holden, D., Myles, D. A. A., Volanakis, J. E., Larry J.DeLucas, L. J., Greenhough, T. J. (2002), The three-dimensional structure of calcium-depleted human C-reactive protein from perfectly twinned crystals, Acta Cryst., D58 :992-1001</ref> | 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">Ramadan, M. A. M., Shrive, A. K., Holden, D., Myles, D. A. A., Volanakis, J. E., Larry J.DeLucas, L. J., Greenhough, T. J. (2002), The three-dimensional structure of calcium-depleted human C-reactive protein from perfectly twinned crystals, Acta Cryst., D58 :992-1001</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. | + | 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"/> |
=== PC binding site === | === PC binding site === | ||
Revision as of 00:00, 27 January 2016
| This Sandbox is Reserved from 15/12/2015, through 15/06/2016 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1120 through Sandbox Reserved 1159. |
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Human C-reactive protein complexed with phosphocholine
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References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Kumar, S. V., Ravunny, R. K., Chakraborty, C. (2011), Conserved Domains, Conserved Residues, and Surface Cavities of C-reactive Protein (CRP), Appl Biochem Biotechnol, 165:497–505
- ↑ http://www.uniprot.org/uniprot/P02741
- ↑ http://www.unco.edu/nhs/Chemistry/faculty/dong/pub/pentraxin.pdf
- ↑ 6.0 6.1 6.2 Thompson, D., Pepys, M. B., Wood, S. P. (1999), The physiological structure of human C-reactive protein and its complex with phosphocholine, Structure February 1999, 7:169–177.
- ↑ 7.0 7.1 A. Agrawal, P. P. Singh, B. Bottazzi, C. Garlanda, A. Mantovani, Pattern recognition by Pentraxins, Adv Exp Med Biol. 2009; 653: 98-116
- ↑ Ramadan, M. A. M., Shrive, A. K., Holden, D., Myles, D. A. A., Volanakis, J. E., Larry J.DeLucas, L. J., Greenhough, T. J. (2002), The three-dimensional structure of calcium-depleted human C-reactive protein from perfectly twinned crystals, Acta Cryst., D58 :992-1001
