1tqc: Difference between revisions
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'''Ovine recombinant PrP(114-234), ARR variant in complex with the VRQ14 Fab fragment (IgG2a)''' | {{Structure | ||
|PDB= 1tqc |SIZE=350|CAPTION= <scene name='initialview01'>1tqc</scene>, resolution 2.80Å | |||
|SITE= | |||
|LIGAND= | |||
|ACTIVITY= | |||
|GENE= PRNP sheep ARR variant ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9940 Ovis aries]) | |||
}} | |||
'''Ovine recombinant PrP(114-234), ARR variant in complex with the VRQ14 Fab fragment (IgG2a)''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1TQC is a [ | 1TQC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TQC OCA]. | ||
==Reference== | ==Reference== | ||
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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15240887 15240887] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Ovis aries]] | [[Category: Ovis aries]] | ||
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[[Category: prion]] | [[Category: prion]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:21:46 2008'' | ||
Revision as of 15:21, 20 March 2008
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| , resolution 2.80Å | |||||||
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| Gene: | PRNP sheep ARR variant (Ovis aries) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Ovine recombinant PrP(114-234), ARR variant in complex with the VRQ14 Fab fragment (IgG2a)
OverviewOverview
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.
About this StructureAbout this Structure
1TQC is a Single protein structure of sequence from Mus musculus and Ovis aries. Full crystallographic information is available from OCA.
ReferenceReference
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
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