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

Peter Mastrangelo; Louise Serpell; Tim Dafforn; Arthur Lesk; Paul Fraser; David Westaway

doi:10.1016/S0014-5793(02)03614-1

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

Peter Mastrangelo, Louise Serpell, Tim Dafforn, Arthur Lesk, Paul Fraser, David Westaway

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	21-26
Number of pages	6
Journal	FEBS Letters
Volume	532
Issue number	1-2
DOIs	https://doi.org/10.1016/S0014-5793(02)03614-1
State	Published - Dec 4 2002

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(02)03614-1

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title = "A cluster of familial Creutzfeldt-Jakob disease mutations recapitulate conserved residues in Doppel: A case of molecular mimicry?",

abstract = "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 PrPC 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 PrPC 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.",

author = "Peter Mastrangelo and Louise Serpell and Tim Dafforn and Arthur Lesk and Paul Fraser and David Westaway",

note = "Funding Information: We thank Jennifer Griffin for helpful comments. P.M. is a Peterborough-Burgess Fellow of the Alzheimer Society of Ontario and this work was supported by grants to D.W. from the Canadian Institutes of Health Research (MOP363377 and MSC 46763). A.M.L., T.D. and L.C.S. are supported by the Wellcome Trust.",

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doi = "10.1016/S0014-5793(02)03614-1",

language = "English (US)",

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T1 - A cluster of familial Creutzfeldt-Jakob disease mutations recapitulate conserved residues in Doppel

T2 - A case of molecular mimicry?

AU - Mastrangelo, Peter

AU - Serpell, Louise

AU - Dafforn, Tim

AU - Lesk, Arthur

AU - Fraser, Paul

AU - Westaway, David

N1 - Funding Information: We thank Jennifer Griffin for helpful comments. P.M. is a Peterborough-Burgess Fellow of the Alzheimer Society of Ontario and this work was supported by grants to D.W. from the Canadian Institutes of Health Research (MOP363377 and MSC 46763). A.M.L., T.D. and L.C.S. are supported by the Wellcome Trust.

PY - 2002/12/4

Y1 - 2002/12/4

N2 - 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 PrPC 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 PrPC 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.

AB - 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 PrPC 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 PrPC 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.

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

Abstract

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