3O79

Crystal Structure of Wild-type Rabbit PrP 126-230

3O79 の概要

• エントリーDOI: 10.2210/pdb3o79/pdb
• 分子名称: Rabbit PrP, SODIUM ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: prp, prion, membrane protein
• 由来する生物種: Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25320.67

構造登録者

Sweeting, B.,Chakrabartty, A.,Pai, E.F. (登録日: 2010-07-30, 公開日: 2010-11-24, 最終更新日: 2024-10-16)

主引用文献

Khan, M.Q.,Sweeting, B.,Mulligan, V.K.,Arslan, P.E.,Cashman, N.R.,Pai, E.F.,Chakrabartty, A.
Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP.
Proc.Natl.Acad.Sci.USA, 107:19808-19813, 2010

PubMed Abstract: Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrP(Sc)). Exposure to PrP(Sc) from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer-octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease.

PubMed: 21041683
DOI: 10.1073/pnas.1005267107

実験手法

X-RAY DIFFRACTION (1.6 Å)