2KTM

Solution NMR structure of H2H3 domain of ovine prion protein (residues 167-234)

Summary for 2KTM

• Entry DOI: 10.2210/pdb2ktm/pdb
• Related: 1tpx 1tqb 1xyu 1y2s
• Descriptor: Major prion protein (1 entity in total)
• Functional Keywords: h2h3, prion protein, peptide folding, fibrilization core, cell membrane, membrane, prion, membrane protein
• Biological source: Ovis aries (domestic sheep,lambs,wild sheep)
• Total number of polymer chains: 1
• Total formula weight: 10244.29

Authors

Pastore, A.,Adrover, M.,Pauwels, K.,de Chiara, C.,Prigent, S.,Rezeai, H. (deposition date: 2010-02-04, release date: 2010-04-07, Last modification date: 2024-10-30)

Primary citation

Adrover, M.,Pauwels, K.,Prigent, S.,de Chiara, C.,Xu, Z.,Chapuis, C.,Pastore, A.,Rezaei, H.
Prion fibrillization is mediated by a native structural element that comprises helices H2 and H3.
J.Biol.Chem., 285:21004-21012, 2010

PubMed Abstract: Aggregation and misfolding of the prion protein (PrP) are thought to be the cause of a family of lethal neurodegenerative diseases affecting humans and other animals. Although the structures of PrP from several species have been solved, still little is known about the mechanisms that lead to the misfolded species. Here, we show that the region of PrP comprising the hairpin formed by the helices H2 and H3 is a stable independently folded unit able to retain its secondary and tertiary structure also in the absence of the rest of the sequence. We also prove that the isolated H2H3 is highly fibrillogenic and forms amyloid fibers morphologically similar to those obtained for the full-length protein. Fibrillization of H2H3 but not of full-length PrP is concomitant with formation of aggregates. These observations suggest a "banana-peeling" mechanism for misfolding of PrP in which H2H3 is the aggregation seed that needs to be first exposed to promote conversion from a helical to a beta-rich structure.

PubMed: 20375014
DOI: 10.1074/jbc.M110.111815

Experimental method

SOLUTION NMR