1OEI

Human prion protein 61-84

Summary for 1OEI

• Entry DOI: 10.2210/pdb1oei/pdb
• Related: 1E1G 1E1J 1E1P 1E1S 1E1U 1E1W 1FKC 1FO7 1H0L 1HJM 1HJN 1I4M 1OEH 1QLX 1QLZ 1QM0 1QM1 1QM2 1QM3
• Descriptor: MAJOR PRION PROTEIN (1 entity in total)
• Functional Keywords: prion protein, octapeptide repeats, protein aggregation, ph-dependent conformation, brain, disease mutation
• 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: 2351.44

Authors

Zahn, R. (deposition date: 2003-03-27, release date: 2004-05-06, Last modification date: 2024-05-15)

Primary citation

Zahn, R.
The Octapeptide Repeats in Mammalian Prion Protein Constitute a Ph-Dependent Folding and Aggregation Site
J.Mol.Biol., 334:477-, 2003

PubMed Abstract: Structural studies of mammalian prion protein at pH values between 4.5 and 5.5 established that the N-terminal 100 residue domain is flexibly disordered. Here, we show that at pH values between 6.5 and 7.8, i.e. the pH at the cell membrane, the octapeptide repeats in recombinant human prion protein hPrP(23-230) encompassing the highly conserved amino acid sequence PHGGGWGQ are structured. The nuclear magnetic resonance solution structure of the octapeptide repeats at pH 6.2 reveals a new structural motif that causes a reversible pH-dependent PrP oligomerization. Within the aggregation motif the segments HGGGW and GWGQ adopt a loop conformation and a beta-turn-like structure, respectively. Comparison with the crystal structure of HGGGW-Cu(2+) indicates that the binding of copper ions induces a conformational transition that presumably modulates PrP aggregation. The knowledge that the cellular prion protein is immobilized on the cell surface along with our results suggests a functional role of aggregation in endocytosis or homophilic cell adhesion.

PubMed: 14623188
DOI: 10.1016/J.JMB.2003.09.048

Experimental method

SOLUTION NMR