2M1J

Ovine Doppel Signal peptide (1-30)

2M1J の概要

• エントリーDOI: 10.2210/pdb2m1j/pdb
• 関連するPDBエントリー: 1SKH 1Z65
• NMR情報: BMRB: 18865
• 分子名称: Prion-like protein doppel (1 entity in total)
• 機能のキーワード: prion-like protein, unknown function
• 由来する生物種: Ovis aries (sheep)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor (By similarity): Q9GJY2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3321.13

構造登録者

Pimenta, J.,Viegas, A.,Sardinha, J.,Santos, A.,Cantante, C.,Dias, F.M.V.,Soares, R.,Cabrita, E.J.,Fontes, C.M.G.A.,Prates, J.A.M.,Pereira, R.M.L.N. (登録日: 2012-11-28, 公開日: 2013-10-16, 最終更新日: 2024-05-15)

主引用文献

Pimenta, J.,Viegas, A.,Sardinha, J.,Martins, I.C.,Cabrita, E.J.,Fontes, C.M.,Prates, J.A.,Pereira, R.M.
NMR solution structure and SRP54M predicted interaction of the N-terminal sequence (1-30) of the ovine Doppel protein.
Peptides, 49C:32-40, 2013

PubMed Abstract: Prion protein (PrP(C)) biosynthesis involves a multi-step process that includes translation and post-translational modifications. While PrP has been widely investigated, for the homolog Doppel (Dpl), limited knowledge is available. In this study, we focused on a vital step of eukaryotic protein biosynthesis: targeting by the signal recognition particle (SRP). Taking the ovine Dpl (OvDpl(1-30)) peptide as a template, we studied its behavior in two different hydrophobic environments using CD and NMR spectroscopy. In both trifluoroethanol (TFE) and dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC), the OvDpl(1-30) peptide revealed to fold in an alpha-helical conformation with a well-defined central region extending from residue Cys8 until Ser22. The NMR structure was subsequently included in a computational docking complex with the conserved M-domain of SRP54 protein (SRP54M), and further compared with the N-terminal structures of mouse Dpl and bovine PrP(C) proteins. This allowed the determination of (i) common predicted N-terminal/SRP54M polar contacts (Asp331, Gln335, Glu365 and Lys432) and (ii) different N-C orientations between prion and Dpl peptides at the SRP54M hydrophobic groove, that are in agreement with each peptide electrostatic potential. Together, these findings provide new insights into the biosynthesis of prion-like proteins. Besides they also show the role of protein conformational switches in signalization toward the endoplasmic membrane, a key event of major significance in the cell cycle. They are thus of general applicability to the study of the biological function of prion-like as well as other proteins.

PubMed: 23973967
DOI: 10.1016/j.peptides.2013.08.013

実験手法

SOLUTION NMR