1UW3

The crystal structure of the globular domain of sheep prion protein

1UW3 の概要

• エントリーDOI: 10.2210/pdb1uw3/pdb
• 関連するPDBエントリー: 1G04 1M25
• 分子名称: PRION PROTEIN, GLUTATHIONE, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: transmissible spongiform encephalopathy, creutzfeld jacob disease, membrane protein
• 由来する生物種: OVIS ARIES (SHEEP)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P23907
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13011.30

構造登録者

Haire, L.F.,Whyte, S.M.,Vasisht, N.,Gill, A.C.,Verma, C.,Dodson, E.J.,Dodson, G.G.,Bayley, P.M. (登録日: 2004-01-29, 公開日: 2004-03-25, 最終更新日: 2023-12-13)

主引用文献

Haire, L.F.,Whyte, S.M.,Vasisht, N.,Gill, A.C.,Verma, C.,Dodson, E.J.,Dodson, G.G.,Bayley, P.M.
The Crystal Structure of the Globular Domain of Sheep Prion Protein
J.Mol.Biol., 336:1175-, 2004

PubMed Abstract: The prion protein PrP is a naturally occurring polypeptide that becomes transformed from a normal conformation to that of an aggregated form, characteristic of pathological states in fatal transmissible spongiform conditions such as Creutzfeld-Jacob Disease and Bovine Spongiform Encephalopathy. We report the crystal structure, at 2 A resolution, of residues 123-230 of the C-terminal globular domain of the ARQ allele of sheep prion protein (PrP). The asymmetric unit contains a single molecule whose secondary structure and overall organisation correspond to those structures of PrPs from various mammalian species determined by NMR. The globular domain shows a close association of helix-1, the C-terminal portion of helix-2 and the N-terminal portion of helix-3, bounded by the intramolecular disulphide bond, 179-214. The loop 164-177, between beta2 and helix-2 is relatively well structured compared to the human PrP NMR structure. Analysis of the sheep PrP structure identifies two possible loci for the initiation of beta-sheet mediated polymerisation. One of these comprises the beta-strand, residues 129-131 that forms an intra-molecular beta-sheet with residues 161-163. This strand is involved in lattice contacts about a crystal dyad to generate a four-stranded intermolecular beta-sheet between neighbouring molecules. The second locus involves the region 188-204, which modelling suggests is able to undergo a partial alpha-->beta switch within the monomer. These loci provide sites within the PrPc monomer that could readily give rise to early intermediate species on the pathway to the formation of aggregated PrPSc containing additional intermolecular beta-structure.

PubMed: 15037077
DOI: 10.1016/J.JMB.2003.12.059

実験手法

X-RAY DIFFRACTION (2.05 Å)