DOI: 10.1073/pnas.051627998. Two different neurodegenerative diseases caused by proteins with similar structures

Two different neurodegenerative diseases caused by proteins with similar structures

10.1073/pnas.051627998

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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

Bibliography

Mo, H., Moore, R. C., Cohen, F. E., Westaway, D., Prusiner, S. B., Wright, P. E., & Dyson, H. J. (2001). Two different neurodegenerative diseases caused by proteins with similar structures. Proceedings of the National Academy of Sciences, 98(5), 2352â2357.

Authors 7

Huaping Mo (first)
Richard C. Moore (additional)
Fred E. Cohen (additional)
David Westaway (additional)
Stanley B. Prusiner (additional)
Peter E. Wright (additional)
H. Jane Dyson (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:45 a.m.)
Deposited	3 years, 2 months ago (June 7, 2022, 1:28 a.m.)
Indexed	1 month, 4 weeks ago (July 2, 2025, 2:31 p.m.)
Issued	24 years, 6 months ago (Feb. 27, 2001)
Published	24 years, 6 months ago (Feb. 27, 2001)
Published Online	24 years, 6 months ago (Feb. 27, 2001)
Published Print	24 years, 6 months ago (Feb. 27, 2001)

Funders 0

None

BibTeX

@article{Mo_2001, title={Two different neurodegenerative diseases caused by proteins with similar structures}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.051627998}, DOI={10.1073/pnas.051627998}, number={5}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Mo, Huaping and Moore, Richard C. and Cohen, Fred E. and Westaway, David and Prusiner, Stanley B. and Wright, Peter E. and Dyson, H. Jane}, year={2001}, month=feb, pages={2352–2357} }

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  "abstract": "<jats:p>\n            The downstream prion-like protein (doppel, or Dpl) is a paralog of\n the cellular prion protein, PrP\n            <jats:sup>C</jats:sup>\n            . The two proteins have\n \u224825% sequence identity, but seem to have distinct physiologic roles.\n Unlike PrP\n            <jats:sup>C</jats:sup>\n            , Dpl does not support prion replication;\n instead, overexpression of Dpl in the brain seems to cause a completely\n different neurodegenerative disease. We report the solution structure\n of a fragment of recombinant mouse Dpl (residues 26\u2013157) containing a\n globular domain with three helices and a small amount of \u03b2-structure.\n Overall, the topology of Dpl is very similar to that of\n PrP\n            <jats:sup>C</jats:sup>\n            . Significant differences include a marked kink in one\n of the helices in Dpl, and a different orientation of the two short\n \u03b2-strands. Although the two proteins most likely arose through\n duplication of a single ancestral gene, the relationship is now so\n distant that only the structures retain similarity; the functions have\n diversified along with the sequence.\n          </jats:p>",
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