DOI: 10.1016/s0014-5793(01)02785-5. Homodimerization of presenilin N‐terminal fragments is affected by mutations linked to Alzheimer's disease

Homodimerization of presenilin N‐terminal fragments is affected by mutations linked to Alzheimer's disease

10.1016/s0014-5793(01)02785-5

Crossref journal-article

Wiley

FEBS Letters (311)

Abstract

Mutations on human presenilins 1 and 2 cause dominant early‐onset familial Alzheimer's disease (FAD). Presenilins are polytopic transmembrane proteins endoproteolytically processed in vivo to N‐ and C‐terminal fragments (NTFs and CTFs). The functional presenilin unit consists of a high molecular weight complex that contains both fragments. Here we show NTF:NTF, CTF:CTF and NTF:CTF interactions by yeast two‐hybrid and in vivo endoplasmic reticulum split‐ubiquitin assays. Our results also highlight the involvement of HL1 – the hydrophilic loop between TMI and TMII – in the NTF:NTF binding site. Besides, nine FAD‐linked presenilin mutations substantially affected HL1:HL1 binding. From the evidence of NTF and CTF homodimerization, we propose the contribution of two NTFs and two CTFs, instead of a single NTF:CTF heterodimer, to the functional presenilin–γ‐secretase complex and that FAD mutations affect the assembly or stability of this complex.

Bibliography

Cervantes, S., GonzÃ lez-Duarte, R., & Marfany, G. (2001). Homodimerization of presenilin Nâterminal fragments is affected by mutations linked to Alzheimerâs disease. FEBS Letters, 505(1), 81â86. Portico.

Authors 3

Sara Cervantes (first)
Roser Gonzàlez-Duarte (additional)
Gemma Marfany (additional)

References 25 Referenced 43

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{'key': 'e_1_2_5_21_1', 'first-page': '353', 'volume': '5', 'author': 'Schwartz R.M', 'year': '1978', 'journal-title': 'Atlas Protein Seq. Struct.'} / Atlas Protein Seq. Struct. by Schwartz R.M (1978)
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Dates

Type	When
Created	22 years, 10 months ago (Oct. 14, 2002, 11:56 a.m.)
Deposited	1 year, 11 months ago (Sept. 16, 2023, 5:33 a.m.)
Indexed	11 months ago (Sept. 16, 2024, 4:08 p.m.)
Issued	24 years ago (Aug. 20, 2001)
Published	24 years ago (Aug. 20, 2001)
Published Online	24 years ago (Aug. 20, 2001)
Published Print	23 years, 11 months ago (Sept. 7, 2001)

Funders 0

None

BibTeX

@article{Cervantes_2001, title={Homodimerization of presenilin N‐terminal fragments is affected by mutations linked to Alzheimer’s disease}, volume={505}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/s0014-5793(01)02785-5}, DOI={10.1016/s0014-5793(01)02785-5}, number={1}, journal={FEBS Letters}, publisher={Wiley}, author={Cervantes, Sara and Gonzàlez-Duarte, Roser and Marfany, Gemma}, year={2001}, month=aug, pages={81–86} }

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