3O79
Crystal Structure of Wild-type Rabbit PrP 126-230
Summary for 3O79
| Entry DOI | 10.2210/pdb3o79/pdb |
| Descriptor | Rabbit PrP, SODIUM ION, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | prp, prion, membrane protein |
| Biological source | Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits) |
| Total number of polymer chains | 2 |
| Total formula weight | 25320.67 |
| Authors | Sweeting, B.,Chakrabartty, A.,Pai, E.F. (deposition date: 2010-07-30, release date: 2010-11-24, Last modification date: 2024-10-16) |
| Primary citation | 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 Cited by 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: 21041683DOI: 10.1073/pnas.1005267107 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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