4TUT

Structure of a Prion peptide

Summary for 4TUT

• Entry DOI: 10.2210/pdb4tut/pdb
• Related: 4UBY 4UBZ 4W5L 4W5M 4W5P 4W5Y 4W67 4W71 4WBU 4WBV
• Descriptor: Prion peptide: GLY-GLY-TYR-MET-LEU-GLY (2 entities in total)
• Functional Keywords: prion peptide, membrane protein, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 596.70

Authors

Yu, L.,Lee, S.-J.,Yee, V. (deposition date: 2014-06-24, release date: 2015-05-27, Last modification date: 2023-12-27)

Primary citation

Yu, L.,Lee, S.J.,Yee, V.C.
Crystal Structures of Polymorphic Prion Protein beta 1 Peptides Reveal Variable Steric Zipper Conformations.
Biochemistry, 54:3640-3648, 2015

PubMed Abstract: The pathogenesis of prion diseases is associated with the conformational conversion of normal, predominantly α-helical prion protein (PrP(C)) into a pathogenic form that is enriched with β-sheets (PrP(Sc)). Several PrP(C) crystal structures have revealed β1-mediated intermolecular sheets, suggesting that the β1 strand may contribute to a possible initiation site for β-sheet-mediated PrP(Sc) propagation. This β1 strand contains the polymorphic residue 129 that influences disease susceptibility and phenotype. To investigate the effect of the residue 129 polymorphism on the conformation of amyloid-like continuous β-sheets formed by β1, crystal structures of β1 peptides containing each of the polymorphic residues were determined. To probe the conformational influence of the peptide construct design, four different lengths of β1 peptides were studied. From the 12 peptides studied, 11 yielded crystal structures ranging in resolution from 0.9 to 1.4 Å. This ensemble of β1 crystal structures reveals conformational differences that are influenced by both the nature of the polymorphic residue and the extent of the peptide construct, indicating that comprehensive studies in which peptide constructs vary are a more rigorous approach to surveying conformational possibilities.

PubMed: 25978088
DOI: 10.1021/acs.biochem.5b00425

Experimental method

X-RAY DIFFRACTION (0.9 Å)