English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The protonation state of histidine 111 regulates the aggregation of the evolutionary most conserved region of the human prion protein.

Fonseca-Ornelas, L., & Zweckstetter, M. (2016). The protonation state of histidine 111 regulates the aggregation of the evolutionary most conserved region of the human prion protein. Protein Science, 25(8), 1563-1567. doi:10.1002/pro.2947.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-2312-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-2315-4
Genre: Journal Article

Files

show Files
hide Files
:
2328559.pdf (Publisher version), 850KB
 
File Permalink:
-
Name:
2328559.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), Göttingen; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Fonseca-Ornelas, L.1, Author              
Zweckstetter, M.1, Author              
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

Content

show
hide
Free keywords: prion protein; NMR spectroscopy; amyloid; misfolding
 Abstract: In a group of neurodegenerative diseases, collectively termed transmissible spongiform encephalopathies, the prion protein aggregates into -sheet rich amyloid-like deposits. Because amyloid structure has been connected to different prion strains and cellular toxicity, it is important to obtain insight into the structural properties of prion fibrils. Using a combination of solution NMR spectroscopy, thioflavin-T fluorescence and electron microscopy we here show that within amyloid fibrils of a peptide containing residues 108-143 of the human prion protein [humPrP (108-143)]the evolutionary most conserved part of the prion protein - residue H111 and S135 are in close spatial proximity and their interaction is critical for fibrillization. We further show that residues H111 and H140 share the same microenvironment in the unfolded, monomeric state of the peptide, but not in the fibrillar form. While protonation of H140 has little influence on fibrillization of humPrP (108-143), a positive charge at position 111 blocks the conformational change, which is necessary for amyloid formation of humPrP (108-143). Our study thus highlights the importance of protonation of histidine residues for protein aggregation and suggests point mutations to probe the structure of infectious prion particles.

Details

show
hide
Language(s): eng - English
 Dates: 2016-06-012016-08
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/pro.2947
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Protein Science
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 25 (8) Sequence Number: - Start / End Page: 1563 - 1567 Identifier: -