Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Structure of the recombinant full-length hamster prion protein PrP(29-231): the N terminus is highly flexible

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Donne, D. G.
  • Viles, J. H.
  • Groth, D.
  • Mehlhorn, I.
  • James, T. L.
  • Cohen, F. E.
  • Prusiner, S. B.
  • Wright, Peter
  • Dyson, Jane

publication date

  • December 1997

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • The prion diseases seem to be caused by a conformational change of the prion protein (PrP) from the benign cellular form PrPC to the infectious scrapie form PrPSc; thus, detailed information about PrP structure may provide essential insights into the mechanism by which these diseases develop. In this study, the secondary structure of the recombinant Syrian hamster PrP of residues 29-231 [PrP(29-231)] is investigated by multidimensional heteronuclear NMR. Chemical shift index analysis and nuclear Overhauser effect data show that PrP(29-231) contains three helices and possibly one short beta-strand. Most striking is the random-coil nature of chemical shifts for residues 30-124 in the full-length PrP. Although the secondary structure elements are similar to those found in mouse PrP fragment PrP(121-231), the secondary structure boundaries of PrP(29-231) are different from those in mouse PrP(121-231) but similar to those found in the structure of Syrian hamster PrP(90-231). Comparison of resonance assignments of PrP(29-231) and PrP(90-231) indicates that there may be transient interactions between the additional residues and the structured core. Backbone dynamics studies done by using the heteronuclear [1H]-15N nuclear Overhauser effect indicate that almost half of PrP(29-231), residues 29-124, is highly flexible. This plastic region could feature in the conversion of PrPC to PrPSc by template-assisted formation of beta-structure.

subject areas

  • Amino Acid Sequence
  • Animals
  • Cricetinae
  • Escherichia coli
  • Magnetic Resonance Spectroscopy
  • Mesocricetus
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments
  • PrPC Proteins
  • PrPSc Proteins
  • Prions
  • Protein Structure, Secondary
  • Recombinant Proteins
  • Species Specificity
  • Thermodynamics
scroll to property group menus

Research

keywords

  • NMR structure
  • backbone dynamics
  • conformational change
scroll to property group menus

Identity

PubMed Central ID

  • PMC28326

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.94.25.13452

PubMed ID

  • 9391046
scroll to property group menus

Additional Document Info

start page

  • 13452

end page

  • 13457

volume

  • 94

issue

  • 25

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support