A cluster of familial Creutzfeldt–Jakob disease mutations recapitulate conserved residues in Doppel: a case of molecular mimicry?

FEBS Letters

Fraser, Paul²  Lesk, Arthur¹  Serpell, Louise¹  Dafforn, Tim¹  Westaway, David²  Mastrangelo, Peter² 

[1] University of Cambridge, Structural Medicine Unit, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, UK;Centre for Research in Neurodegenerative Diseases, University of Toronto, Tanz Neuroscience Building, 6 Queen's Park Crescent West, Toronto, ON, Canada M5S 3H2

关键词: Paralog cross-talk;    Prion;    Molecular mimicry;   

DOI  :  10.1016/S0014-5793(02)03614-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Intrachromosomal deletions linking Dpl expression to the PrP promoter produce cerebellar degeneration that can be abrogated by the introduction of wild-type PrP transgenes. Since Dpl-like truncated forms of PrP are neuropathogenic in mice and likewise counterbalanced by expression of PrP^C we asked whether naturally occurring mutant forms of human PrP have Dpl-like attributes. Five PRNP missense mutations causing familial Creutzfeldt–Jakob disease (F-CJD) map to a helical region found in both PrP^C and Dpl and result in amino acids identical to conserved residues in Dpl. These F-CJD alleles may cause mutant PrP to become a weak mimetic of Dpl structure and/or function.

【 授权许可】

Unknown