Two different neurodegenerative diseases caused by proteins with similar structures


Autoria(s): Mo, Huaping; Moore, Richard C.; Cohen, Fred E.; Westaway, David; Prusiner, Stanley B.; Wright, Peter E.; Dyson, H. Jane
Data(s)

27/02/2001

Resumo

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, 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 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.

Identificador

/pmc/articles/PMC30142/

/pubmed/11226243

http://dx.doi.org/10.1073/pnas.051627998

Idioma(s)

en

Publicador

The National Academy of Sciences

Direitos

Copyright © 2001, The National Academy of Sciences

Palavras-Chave #Biological Sciences
Tipo

Text