Two Different Neurodegenerative Diseases Caused by Proteins with Similar Structures

The downstream prion-like protein (doppel, or Dpl) is a paralog of the cellular prion protein, PrPC. The two proteins have ≈25% sequence identity, but seem to have distinct physiologic roles. Unlike PrPC, Dpl does not support prion replication; instead, over-expression of Dpl in the brain seems to c...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-02, Vol.98 (5), p.2352-2357
Main Authors: Mo, Huaping, Moore, Richard C., Cohen, Fred E., Westaway, David, Prusiner, Stanley B., Wright, Peter E., Dyson, H. Jane
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Biological Sciences
Biology
Chemical bonding
Chemical equilibrium
Cloning, Molecular
Disulfides
Disulfides - chemistry
DNA Primers
Dpl protein
GPI-Linked Proteins
Humans
Models, Molecular
Molecular Sequence Data
Molecular structure
Neurodegenerative diseases
Neurodegenerative Diseases - etiology
Neurodegenerative Diseases - metabolism
Neurological disorders
Nuclear Magnetic Resonance, Biomolecular
Physics
Prion diseases
Prions
Prions - chemistry
Prions - genetics
Prions - physiology
Protein Conformation
Protein refolding
Proteins
PrPC Proteins - chemistry
PrPC Proteins - physiology
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Sequence Homology, Amino Acid
Topology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The downstream prion-like protein (doppel, or Dpl) is a paralog of the cellular prion protein, PrPC. The two proteins have ≈25% sequence identity, but seem to have distinct physiologic roles. Unlike PrPC, Dpl does not support prion replication; instead, over-expression of Dpl in the brain seems to cause a completely different neurodegenerative disease. We report the solution structure of a fragment of recombinant mouse Dpl (residues 26-157) containing a globular domain with three helices and a small amount of β-structure. Overall, the topology of Dpl is very similar to that of PrPC. Significant differences include a marked kink in one of the helices in Dpl, and a different orientation of the two short β-strands. Although the two proteins most likely arose through duplication of a single ancestral gene, the relationship is now so distant that only the structures retain similarity; the functions have diversified along with the sequence.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.051627998