Sandbox207: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Elise Rosati (talk | contribs) No edit summary |
Elise Rosati (talk | contribs) No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 23: | Line 23: | ||
:The CRP gene is located on '''chromosome 1q23'''. It is composed of '''two exons''' and '''one intron'''. This gene is regulated by interleukin-6, the principal inducer of the gene during the acute phase. CRP is secreted by '''hepatocytes'''.[http://www.rndsystems.com/cb_detail_objectname_SU05_CReactiveProtein.aspx <1>] | :The CRP gene is located on '''chromosome 1q23'''. It is composed of '''two exons''' and '''one intron'''. This gene is regulated by interleukin-6, the principal inducer of the gene during the acute phase. CRP is secreted by '''hepatocytes'''.[http://www.rndsystems.com/cb_detail_objectname_SU05_CReactiveProtein.aspx <1>] | ||
:The Human CRP belongs to the '''pentraxin family''' , proteins having five identical, non-covalently associated subunits that form a symmetrical '''homopentameric ring'''. The pentraxin family is highly conserved in evolution.[http://www.jci.org/articles/view/18921 <3>] | :The Human CRP belongs to the '''pentraxin family''', proteins having five identical, non-covalently associated subunits that form a symmetrical '''homopentameric ring'''. The pentraxin family is highly conserved in evolution.[http://www.jci.org/articles/view/18921 <3>] | ||
===Size=== | ===Size=== | ||
| Line 39: | Line 39: | ||
(a) Negatively stained electron micrograph showing the typical pentameric disc-like structure face-on and side-on (arrows). (b) Ribbon diagram of the crystal structure, showing the lectin fold and the two calcium atoms (spheres) in the ligand-binding site of each protomer. (c) Space-filling model of the CRP molecule, showing a single phosphocholine molecule located in the ligand-binding site of each protomer.[http://www.jci.org/articles/view/18921 <3>]]] | (a) Negatively stained electron micrograph showing the typical pentameric disc-like structure face-on and side-on (arrows). (b) Ribbon diagram of the crystal structure, showing the lectin fold and the two calcium atoms (spheres) in the ligand-binding site of each protomer. (c) Space-filling model of the CRP molecule, showing a single phosphocholine molecule located in the ligand-binding site of each protomer.[http://www.jci.org/articles/view/18921 <3>]]] | ||
: Thanks to this rotation, the alpha-helices can lie closer to the axis of the pentamere, therefore bringing the bound Ca2+ further away from it. On each subunit, we can find '''phosphocholine''' bound in a shallow surface pocket. With the help of phosphate groups and Glu81 via the choline moiety | : Thanks to this rotation, the alpha-helices can lie closer to the axis of the pentamere, therefore bringing the bound Ca2+ further away from it. On each subunit, we can find '''phosphocholine''' bound in a shallow surface pocket. With the help of phosphate groups and Glu81 via the choline moiety, the phosphocholine can '''interact''' with the two protein-bound ions. | ||
:Moreover, the structure of CRP is different in ill patients. Indeed, '''in some pathological conditions''', the Human CRP is '''glycosylated'''. Analysis of the structure showed the systematic '''absence of two peptide fragments''', one at the N-terminus (loop 1-6) in all patients, the other near the C-terminus (loop 189-191) in patients with '''osteogenic sarcoma and Cushing's syndrome'''. In a healthy individual, '''glycosylation sites are inacessible due to the presence of the N-terminal'''. The loss of these two fragments exposed two potential glycosylation sites on a cleft door. The functional areas of the pentraxin structure remain the same since the Ca2+ and phosphocholine sites are on the opposite site of the pentraxin molecule. [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>] | :Moreover, the structure of CRP is different in ill patients. Indeed, '''in some pathological conditions''', the Human CRP is '''glycosylated'''. Analysis of the structure showed the systematic '''absence of two peptide fragments''', one at the N-terminus (loop 1-6) in all patients, the other near the C-terminus (loop 189-191) in patients with '''osteogenic sarcoma and Cushing's syndrome'''. In a healthy individual, '''glycosylation sites are inacessible due to the presence of the N-terminal'''. The loss of these two fragments exposed two potential glycosylation sites on a cleft door. The functional areas of the pentraxin structure remain the same since the Ca2+ and phosphocholine sites are on the opposite site of the pentraxin molecule. [http://biology.kenyon.edu/BMB/Chime2/2005/Jenny/FRAMES/ <2>] | ||
| Line 60: | Line 60: | ||
<Structure load='1b09' size='250' frame='true' align='right' caption='CRP complexed with Phosphocholine' scene='Phosphocholine' /> | <Structure load='1b09' size='250' frame='true' align='right' caption='CRP complexed with Phosphocholine' scene='Phosphocholine' /> | ||
:In the presence of calcium, CRP is '''specifically''' bound to <scene name='Sandbox207/Phosphocholine/9'>phosphocholine </scene> residues. We find phosphocholine in the microbial polysaccharides. | :In the presence of calcium, CRP is '''specifically''' bound to <scene name='Sandbox207/Phosphocholine/9'>phosphocholine </scene> 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'''. | ||
| Line 98: | Line 96: | ||
7- ''C-reactive Protein at the Interface Between Innate Immunity, Inflammation: CRP Structure & Expression'', Andres Peisajovich,1 Lorraine Marnell,2 Carolyn Mold,3 Terry W Du Clos 4. | 7- ''C-reactive Protein at the Interface Between Innate Immunity, Inflammation: CRP Structure & Expression'', Andres Peisajovich,1 Lorraine Marnell,2 Carolyn Mold,3 Terry W Du Clos 4. | ||
[http://www.medscape.com/viewarticle/575924_3 <7>] | [http://www.medscape.com/viewarticle/575924_3 <7>] | ||
== Proteopedia Page Contributors and Editors == | |||
Astrid BUTET and Elise ROSATI | |||
