2N53

Solution structure of ovis aries prp

Summary for 2N53

• Entry DOI: 10.2210/pdb2n53/pdb
• Related: 2MV8 2MV9
• NMR Information: BMRB: 25692
• Descriptor: Major prion protein (1 entity in total)
• Functional Keywords: scrapie, cellular form, transmissible spongiform encephalopathy, cell cycle
• Biological source: Ovis aries (domestic sheep,lambs,wild sheep)
• Cellular location: Cell membrane ; Lipid-anchor, GPI-anchor : Q712V9
• Total number of polymer chains: 1
• Total formula weight: 17541.60

Authors

Munoz, C.,Egalon, A.,Beringue, V.,Rezaei, H.,Dron, M.,Sizun, C. (deposition date: 2015-07-06, release date: 2016-05-25, Last modification date: 2023-06-14)

Primary citation

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

Experimental method

SOLUTION NMR