PDBsum entry 3nhc

Protein fibril

PDB id: 3nhc

Contents

Ligands

GLY-TYR-MET-LEU-GLY-SER ×2

Waters ×4

PDB id:

3nhc

Name:

Protein fibril

Title:

Gymlgs segment 127-132 from human prion with m129

Structure:

Major prion protein. Chain: a, b. Fragment: residues 127-132. Synonym: prp, prp27-30, prp33-35c, ascr. Engineered: yes

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Other_details: gymlgs (residues 127-132 with m129) from human prion protein, synthesized

Resolution:

1.57Å R-factor: 0.225 R-free: 0.253

Authors:

M.I.Apostol,D.Eisenberg

Key ref:

M.I.Apostol et al. (2010). Crystallographic studies of prion protein (PrP) segments suggest how structural changes encoded by polymorphism at residue 129 modulate susceptibility to human prion disease. J Biol Chem, 285, 29671-29675. PubMed id: 20685658 DOI: 10.1074/jbc.C110.158303

Date:

14-Jun-10 Release date: 04-Aug-10

DOI no: 10.1074/jbc.C110.158303

J Biol Chem 285:29671-29675 (2010)

PubMed id: 20685658

Crystallographic studies of prion protein (PrP) segments suggest how structural changes encoded by polymorphism at residue 129 modulate susceptibility to human prion disease.

M.I.Apostol, M.R.Sawaya, D.Cascio, D.Eisenberg.

ABSTRACT

A single nucleotide polymorphism (SNP) in codon 129 of the human prion gene, leading to a change from methionine to valine at residue 129 of prion protein (PrP), has been shown to be a determinant in the susceptibility to prion disease. However, the molecular basis of this effect remains unexplained. In the current study, we determined crystal structures of prion segments having either Met or Val at residue 129. These 6-residue segments of PrP centered on residue 129 are "steric zippers," pairs of interacting β-sheets. Both structures of these "homozygous steric zippers" reveal direct intermolecular interactions between Met or Val in one sheet and the identical residue in the mating sheet. These two structures, plus a structure-based model of the heterozygous Met-Val steric zipper, suggest an explanation for the previously observed effects of this locus on prion disease susceptibility and progression.