1G04

SOLUTION STRUCTURE OF SYNTHETIC 26-MER PEPTIDE CONTAINING 145-169 SHEEP PRION PROTEIN SEGMENT AND C-TERMINAL CYSTEINE

1G04 の概要

• エントリーDOI: 10.2210/pdb1g04/pdb
• NMR情報: BMRB: 4650
• 分子名称: MAJOR PRION PROTEIN (1 entity in total)
• 機能のキーワード: prion, beta hairpin, unknown function
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P23907
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3431.73

構造登録者

Kozin, S.A.,Bertho, G.,Mazur, A.K.,Rabesona, H.,Girault, J.-P.,Haertle, T.,Takahashi, M.,Debey, P.,Hui Bon Hoa, G. (登録日: 2000-10-05, 公開日: 2002-01-23, 最終更新日: 2024-05-22)

主引用文献

Kozin, S.A.,Bertho, G.,Mazur, A.K.,Rabesona, H.,Girault, J.P.,Haertle, T.,Takahashi, M.,Debey, P.,Hoa, G.H.
Sheep prion protein synthetic peptide spanning helix 1 and beta-strand 2 (residues 142-166) shows beta-hairpin structure in solution.
J.Biol.Chem., 276:46364-46370, 2001

PubMed Abstract: According to the "protein only" hypothesis, a conformational conversion of the non-pathogenic "cellular" prion isoform into a pathogenic "scrapie" isoform is the fundamental event in the onset of prion diseases. During this pathogenic conversion, helix H1 and two adjacent surface loops L2 and L3 of the normal prion protein are thought to undergo a conformational transition into an extended beta-like structure, which is prompted by interactions with the pre-existing beta-sheet. To get more insight into the interaction between the helix and one of the beta-strands in the partially unfolded prion protein, the solution structure of a synthetic linear peptide spanning helix H1 and beta-strand S2 (residues 142-166 in human numbering) was studied by circular dichroism and nuclear magnetic resonance spectroscopies. We found that, in contrast to many prion fragments studied earlier, this peptide (i) is highly soluble and does not aggregate up to a millimolar concentration range in aqueous medium and (ii) exhibits an intrinsic propensity to a beta-hairpin like conformation at neutral pH. This beta-propensity can be one of the internal driving forces of the molecular rearrangement responsible for the pathogenic conversion of the prion protein.

PubMed: 11577109
DOI: 10.1074/jbc.M108014200

実験手法

SOLUTION NMR