1HJM

HUMAN PRION PROTEIN AT PH 7.0

Summary for 1HJM

• Entry DOI: 10.2210/pdb1hjm/pdb
• Related: 1E1G 1E1J 1E1P 1E1S 1E1U 1E1W 1HJN
• NMR Information: BMRB: 5713
• Descriptor: MAJOR PRION PROTEIN PRECURSOR (1 entity in total)
• Functional Keywords: prion protein, prion, brain, glycoprotein, gpi-anchor
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 12559.97

Authors

Calzolai, L.,Zahn, R. (deposition date: 2003-02-27, release date: 2003-07-03, Last modification date: 2024-10-09)

Primary citation

Calzolai, L.,Zahn, R.
Influence of Ph on NMR Structure and Stability of the Human Prion Protein Globular Domain
J.Biol.Chem., 278:35592-, 2003

PubMed Abstract: The NMR structure of the globular domain of the human prion protein (hPrP) with residues 121-230 at pH 7.0 shows the same global fold as the previously published structure determined at pH 4.5. It contains three alpha-helices, comprising residues 144-156, 174-194, and 200-228, and a short anti-parallel beta-sheet, comprising residues 128-131 and 161-164. There are slight, strictly localized, conformational changes at neutral pH when compared with acidic solution conditions: helix alpha1 is elongated at the C-terminal end with residues 153-156 forming a 310-helix, and the population of helical structure in the C-terminal two turns of helix alpha 2 is increased. The protonation of His155 and His187 presumably contributes to these structural changes. Thermal unfolding monitored by far UV CD indicates that hPrP-(121-230) is significantly more stable at neutral pH. Measurements of amide proton protection factors map local differences in protein stability within residues 154-157 at the C-terminal end of helix alpha 1 and residues 161-164 of beta-strand 2. These two segments appear to form a separate domain that at acidic pH has a larger tendency to unfold than the overall protein structure. This domain could provide a "starting point" for pH-induced unfolding and thus may be implicated in endosomic PrPC to PrPSc conformational transition resulting in transmissible spongiform encephalopathies.

PubMed: 12826672
DOI: 10.1074/JBC.M303005200

Experimental method

SOLUTION NMR