Sandbox Reserved 474

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==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1gnh' size='500' side='right' caption='Structure of Human C-Reactive Protein (PDB entry [[1gnh]])' scene=''>'''C-Reactive Protein''' (CRP) consists of five identical, non-covalently associated protomers that are arranged in a symmetrical fashion weighing ~ 23kDa as it participates in the systemic response to inflammation. CRP acts as a recognition molecule such that it binds specifically to certain molecular configurations either during cell death or on the surface of exposed pathogens. After an acute inflammatory stimulus, CRP is synthesized by hepatocytes. CRP sits on the short arm of chromosome 1 (in humans) and it contains only one intron and it is regulated at the transcriptional level by '''cytokine interleukin-6''' (IL-6) and by '''interleukin-1β''' (IL-1β). Both IL-6 and IL-1β control expression of many acute phase protein genes through activation of several transcription factors including STAT3, C/EBP family members and Rel proteins (NF-κB).
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==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1gnh' size='500' side='right' caption='Structure of Human C-Reactive Protein (PDB entry [[1gnh]])' scene=''>'''C-Reactive Protein''' (CRP) is a normal plasma protein in which it rises as a cytokine-mediated response resulting from tissue injury, infection or inflammation. It is a a member of the pentraxin family which includes serum amyloid P component (SAP) and it consists of five identical, non-covalently associated protomers that are arranged in a symmetrical fashion weighing ~ 23kDa. CRP acts as a recognition molecule such that it binds specifically to certain molecular configurations either during cell death or on the surface of exposed pathogens. After an acute inflammatory stimulus, CRP is synthesized by hepatocytes. CRP sits on the short arm of chromosome 1 (in humans) and it contains only one intron and it is regulated at the transcriptional level by '''cytokine interleukin-6''' (IL-6) and by '''interleukin-1β''' (IL-1β). Both IL-6 and IL-1β control expression of many acute phase protein genes through activation of several transcription factors including STAT3, C/EBP family members and Rel proteins (NF-κB).
Some of the biological effects/functions of CRP include: CRP's unique ability to only bind to phosphocholine ligands of either damaged or apoptotic cells. Additionally, CRP can bind to other ligands such as phosphoethanolamine, chromatin, histones, fibronectin, small nuclear ribonucleoproteins, laminin, and polycations. CRP also contains pleiotropic effects which produce both pro and anti-inflammatory responses.</StructureSection><!-- PLEASE DO NOT DELETE THIS TEMPLATE -->
Some of the biological effects/functions of CRP include: CRP's unique ability to only bind to phosphocholine ligands of either damaged or apoptotic cells. Additionally, CRP can bind to other ligands such as phosphoethanolamine, chromatin, histones, fibronectin, small nuclear ribonucleoproteins, laminin, and polycations. CRP also contains pleiotropic effects which produce both pro and anti-inflammatory responses.</StructureSection><!-- PLEASE DO NOT DELETE THIS TEMPLATE -->
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The co-crystallized structure of CRP with phosphocholine suggest that Phe-66 and Glu-81 are two key residues that mediate binding between phosphocholine and CRP. More specifically, Phe-66 provides hydrophobic interactions with the methyl groups of phosphocholine. Similarly, Glu-81 is found on the opposite end of the pocket where it interacts well with the positively charged choline nitrogen. Present on the opposite face of the pentamer is the effector face, where the presumed C1q and Fcγ receptors bind
The co-crystallized structure of CRP with phosphocholine suggest that Phe-66 and Glu-81 are two key residues that mediate binding between phosphocholine and CRP. More specifically, Phe-66 provides hydrophobic interactions with the methyl groups of phosphocholine. Similarly, Glu-81 is found on the opposite end of the pocket where it interacts well with the positively charged choline nitrogen. Present on the opposite face of the pentamer is the effector face, where the presumed C1q and Fcγ receptors bind
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== Structure of CRP promoter ==
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Based on homology modeling, CRP structure was found to be similar to that of SAP. The subunits within the structure consisted of a two-layered β sheet with a flattened jelly roll topology. Additionally, there is a presence of two calcium ions that are bound 4 Å apart by protein sidechains, and this is the site of ligand binding, which is referred to as the B side. The other side, designated A hosts a single α, and the pentameric disc shows five helices on one side with ten calcuim ions on the other. The side walls on the A face are constructed from Ser5, Arg6, Gln203, Pro206, Trp187, Arg188, Asn160, Gly177, Leu176, Try175, His95 and Asp112. The bottom side of CRP consiss of ASn158, His38, Leu37, Val94 and Asp112.
== CRP Role in Atherosclerosis ==
== CRP Role in Atherosclerosis ==
Human Recombinant CRP has been determined to serve as a mediator of atherosclerosis. CRP has been shown to initiate IL-6 and endothelin-1 release from endothelial cells
Human Recombinant CRP has been determined to serve as a mediator of atherosclerosis. CRP has been shown to initiate IL-6 and endothelin-1 release from endothelial cells

Revision as of 02:41, 1 May 2012

==Your Heading Here (maybe something like 'Structure')==

Structure of Human C-Reactive Protein (PDB entry 1gnh)

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This Sandbox is Reserved from 13/03/2012, through 01/06/2012 for use in the course "Proteins and Molecular Mechanisms" taught by Robert B. Rose at the North Carolina State University, Raleigh, NC USA. This reservation includes Sandbox Reserved 451 through Sandbox Reserved 500.
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Structure and Function

CRPs five promoter structures are folded into two anti-parallel β-sheets with flattened jellyroll topologies. Each promoter contains a recognition face with a phosphocholine binding site consisting of two coordinated calcium ions adjacent to a hydrophobic pocket. The co-crystallized structure of CRP with phosphocholine suggest that Phe-66 and Glu-81 are two key residues that mediate binding between phosphocholine and CRP. More specifically, Phe-66 provides hydrophobic interactions with the methyl groups of phosphocholine. Similarly, Glu-81 is found on the opposite end of the pocket where it interacts well with the positively charged choline nitrogen. Present on the opposite face of the pentamer is the effector face, where the presumed C1q and Fcγ receptors bind

Structure of CRP promoter

Based on homology modeling, CRP structure was found to be similar to that of SAP. The subunits within the structure consisted of a two-layered β sheet with a flattened jelly roll topology. Additionally, there is a presence of two calcium ions that are bound 4 Å apart by protein sidechains, and this is the site of ligand binding, which is referred to as the B side. The other side, designated A hosts a single α, and the pentameric disc shows five helices on one side with ten calcuim ions on the other. The side walls on the A face are constructed from Ser5, Arg6, Gln203, Pro206, Trp187, Arg188, Asn160, Gly177, Leu176, Try175, His95 and Asp112. The bottom side of CRP consiss of ASn158, His38, Leu37, Val94 and Asp112.

CRP Role in Atherosclerosis

Human Recombinant CRP has been determined to serve as a mediator of atherosclerosis. CRP has been shown to initiate IL-6 and endothelin-1 release from endothelial cells

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