1TQC

Ovine recombinant PrP(114-234), ARR variant in complex with the VRQ14 Fab fragment (IgG2a)

1TQC の概要

• エントリーDOI: 10.2210/pdb1tqc/pdb
• 関連するPDBエントリー: 1TQB
• 分子名称: prion protein, VRQ14 Fab Heavy chain, VRQ14 Fab light chain, ... (4 entities in total)
• 機能のキーワード: prion, antibody, unknown function-immune system complex, unknown function/immune system
• 由来する生物種: Ovis aries (sheep); 詳細
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P23907
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 59163.89

構造登録者

Eghiaian, F.,Grosclaude, J.,Lesceu, S.,Debey, P.,Doublet, B.,Treguer, E.,Rezaei, H.,Knossow, M. (登録日: 2004-06-17, 公開日: 2004-07-06, 最終更新日: 2024-10-23)

主引用文献

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.USA, 101:10254-10259, 2004

PubMed Abstract: 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.

PubMed: 15240887
DOI: 10.1073/pnas.0400014101

実験手法

X-RAY DIFFRACTION (2.8 Å)