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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...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 2001-02, Vol.98 (5), p.2352-2357 |
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| cites | cdi_FETCH-LOGICAL-c516t-89bd1dd1a03b2f1e3d07af410b3aa011fc92d9022964c87400cc84363cfb02b03 |
| container_end_page | 2357 |
| container_issue | 5 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 98 |
| creator | Mo, Huaping Moore, Richard C. Cohen, Fred E. Westaway, David Prusiner, Stanley B. Wright, Peter E. Dyson, H. Jane |
| description | 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. |
| doi_str_mv | 10.1073/pnas.051627998 |
| format | article |
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Jane</creatorcontrib><title>Two Different Neurodegenerative Diseases Caused by Proteins with Similar Structures</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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. 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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2001-02, Vol.98 (5), p.2352-2357 |
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| source | JSTOR Archival Journals and Primary Sources Collection; PubMed Central |
| 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 |
| title | Two Different Neurodegenerative Diseases Caused by Proteins with Similar Structures |
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