2M1J

Ovine Doppel Signal peptide (1-30)

Summary for 2M1J

• Entry DOI: 10.2210/pdb2m1j/pdb
• Related: 1SKH 1Z65
• NMR Information: BMRB: 18865
• Descriptor: Prion-like protein doppel (1 entity in total)
• Functional Keywords: prion-like protein, unknown function
• Biological source: Ovis aries (sheep)
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor (By similarity): Q9GJY2
• Total number of polymer chains: 1
• Total formula weight: 3321.13

Authors

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. (deposition date: 2012-11-28, release date: 2013-10-16, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

SOLUTION NMR