1tqb

From Proteopedia

(Difference between revisions)

Revision as of 08:48, 21 March 2018

Ovine recombinant PrP(114-234), VRQ variant in complex with the Fab of the VRQ14 antibody

Structural highlights

1tqb is a 3 chain structure with sequence from Lk3 transgenic mice and Ovis ammon aries. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1tqc
Gene:	PRNP sheep VRQ variant (Ovis ammon aries)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PRIO_SHEEP] Note=Polymorphism at position 171 may be related to the alleles of scrapie incubation-control (SIC) gene in this species. Note=Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc. Note=Scrapie is a transmissible neurodegenerative disorder of sheep and goats. Most sheep that contract the disease naturally die between 24 and 50 months of age. The incubation period in sheep depends on the strain(s) of the infecting pathogen, sheep age at exposure, and the sheep genotype. The survival time is mainly determined by a single genetic locus, SIP, which has two alleles, susceptible (sa) and resistant (pa). Short incubation period is conferred by the partially dominant sa allele. Scrapie can be spread between flockmates, or it can be transmitted from an infected ewe to its lamb.

Function

[PRIO_SHEEP] May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Prion diseases are associated with the conversion of the alpha-helix rich prion protein (PrPC) into a beta-structure-rich insoluble conformer (PrPSc) that is thought to be infectious. The mechanism for the PrPC-->PrPSc conversion and its relationship with the pathological effects of prion diseases are poorly understood, partly because of our limited knowledge of the structure of PrPSc. In particular, the way in which mutations in the PRNP gene yield variants that confer different susceptibilities to disease needs to be clarified. We report here the 2.5-A-resolution crystal structures of three scrapie-susceptibility ovine PrP variants complexed with an antibody that binds to PrPC and to PrPSc; they identify two important features of the PrPC-->PrPSc conversion. First, the epitope of the antibody mainly consists of the last two turns of ovine PrP second alpha-helix. We show that this is a structural invariant in the PrPC-->PrPSc conversion; taken together with biochemical data, this leads to a model of the conformational change in which the two PrPC C-terminal alpha-helices are conserved in PrPSc, whereas secondary structure changes are located in the N-terminal alpha-helix. Second, comparison of the structures of scrapie-sensitivity variants defines local changes in distant parts of the protein that account for the observed differences of PrPC stability, resistant variants being destabilized compared with sensitive ones. Additive contributions of these sensitivity-modulating mutations to resistance suggest a possible causal relationship between scrapie resistance and lowered stability of the PrP protein.

Insight into the PrPC-->PrPSc conversion from the structures of antibody-bound ovine prion scrapie-susceptibility variants.,Eghiaian F, Grosclaude J, Lesceu S, Debey P, Doublet B, Treguer E, Rezaei H, Knossow M Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10254-9. Epub 2004 Jul 6. PMID:15240887^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Eghiaian F, Grosclaude J, Lesceu S, Debey P, Doublet B, Treguer E, Rezaei H, Knossow M. Insight into the PrPC-->PrPSc conversion from the structures of antibody-bound ovine prion scrapie-susceptibility variants. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10254-9. Epub 2004 Jul 6. PMID:15240887 doi:http://dx.doi.org/10.1073/pnas.0400014101

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1tqb"

@@ Line 1: / Line 1: @@
 ==Ovine recombinant PrP(114-234), VRQ variant in complex with the Fab of the VRQ14 antibody==
 <StructureSection load='1tqb' size='340' side='right' caption='[[1tqb]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tqc|1tqc]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRNP sheep VRQ variant ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9940 Ovis ammon aries])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tqb OCA], [http://pdbe.org/1tqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tqb RCSB], [http://www.ebi.ac.uk/pdbsum/1tqb PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tqb OCA], [http://pdbe.org/1tqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tqb RCSB], [http://www.ebi.ac.uk/pdbsum/1tqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tqb ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tq/1tqb_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tq/1tqb_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 32: / Line 33: @@
 ==See Also==
-*[[Antibody|Antibody]]
+*[[Antibody 3D structures|Antibody 3D structures]]
 *[[Prion|Prion]]
 == References ==

1tqb

From Proteopedia

Revision as of 08:48, 21 March 2018

Ovine recombinant PrP(114-234), VRQ variant in complex with the Fab of the VRQ14 antibody

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox