2M8T

Solution NMR structure of the V209M variant of the human prion protein (residues 90-231)

Summary for 2M8T

• Entry DOI: 10.2210/pdb2m8t/pdb
• NMR Information: BMRB: 19268
• Descriptor: Major prion protein (1 entity in total)
• Functional Keywords: membrane protein, cell cycle
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor. Isoform 2: Cytoplasm: P04156
• Total number of polymer chains: 1
• Total formula weight: 16557.40

Authors

Mills, J.L.,Surewicz, K.,Surewicz, W.,Soennichsen, F.D. (deposition date: 2013-05-28, release date: 2013-09-11, Last modification date: 2024-05-15)

Primary citation

Kong, Q.,Mills, J.L.,Kundu, B.,Li, X.,Qing, L.,Surewicz, K.,Cali, I.,Huang, S.,Zheng, M.,Swietnicki, W.,Sonnichsen, F.D.,Gambetti, P.,Surewicz, W.K.
Thermodynamic Stabilization of the Folded Domain of Prion Protein Inhibits Prion Infection in Vivo.
Cell Rep, 4:248-254, 2013

PubMed Abstract: Prion diseases, or transmissible spongiform encephalopathies (TSEs), are associated with the conformational conversion of the cellular prion protein, PrP(C), into a protease-resistant form, PrP(Sc). Here, we show that mutation-induced thermodynamic stabilization of the folded, α-helical domain of PrP(C) has a dramatic inhibitory effect on the conformational conversion of prion protein in vitro, as well as on the propagation of TSE disease in vivo. Transgenic mice expressing a human prion protein variant with increased thermodynamic stability were found to be much more resistant to infection with the TSE agent than those expressing wild-type human prion protein, in both the primary passage and three subsequent subpassages. These findings not only provide a line of evidence in support of the protein-only model of TSEs but also yield insight into the molecular nature of the PrP(C)→PrP(Sc) conformational transition, and they suggest an approach to the treatment of prion diseases.

PubMed: 23871665
DOI: 10.1016/j.celrep.2013.06.030

Experimental method

SOLUTION NMR