2MV8

Solution structure of Ovis Aries PrP with mutation delta190-197

2MV8 の概要

• エントリーDOI: 10.2210/pdb2mv8/pdb
• NMR情報: BMRB: 25250
• 分子名称: Major prion protein (1 entity in total)
• 機能のキーワード: prion, scrapie, major prion protein, cellular form, transmissible spongiform encephalopathy, immune system
• 由来する生物種: Ovis aries (domestic sheep,lambs,wild sheep)
• 細胞内の位置: Cell membrane ; Lipid-anchor, GPI-anchor : Q712V9
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16669.63

構造登録者

Munoz, C.,Egalon, A.,Beringue, V.,Rezaei, H.,Dron, M.,Sizun, C. (登録日: 2014-09-25, 公開日: 2015-10-07, 最終更新日: 2024-10-09)

主引用文献

Munoz-Montesino, C.,Sizun, C.,Moudjou, M.,Herzog, L.,Reine, F.,Chapuis, J.,Ciric, D.,Igel-Egalon, A.,Laude, H.,Beringue, V.,Rezaei, H.,Dron, M.
Generating Bona Fide Mammalian Prions with Internal Deletions.
J.Virol., 90:6963-6975, 2016

PubMed Abstract: Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions.

PubMed: 27226369
DOI: 10.1128/JVI.00555-16

実験手法

SOLUTION NMR