Oligomerization of human presenilin‐1 fragments

FEBS Letters

Hébert, Sébastien S¹  Lévesque, Georges¹  Godin, Chantal¹ 

[1] Molecular and Human Genetics Unit, CHUQ-Pavillon St-François d'Assise, 10 rue de l'Espinay, Quebec, QC, Canada G1L 3L5

关键词: Presenilin;    γ-secretase;    Homodimerization;    Heterodimerization;    PS1;    presenilin-1;    NTF;    N-terminal fragment;    CTF;    C-terminal fragment;    β-gal;    β-galactosidase;    His;    histidine;    Ade;    adenine;    Trp;    tryptophan;    Leu;    leucine;    TM;    transmembrane;    wt;    wild-type;   

DOI  :  10.1016/S0014-5793(03)00813-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

To gain insight into presenilin-1 (PS1) structural aspects, we explored the structure–function relationship of its N- and C-terminal (NTF and CTF, respectively) complexes. We demonstrated that both NTF and CTF act as independent but inter-changing binding units capable of binding each other (NTF/CTF) or their homologues (NTF/NTF; CTF/CTF). The Alzheimer's disease-associated PS1 mutations Y115H and M146L do not affect their ability to hetero- and/or homodimerize, thus conserving their basic integrity and function(s). These results suggest that PS1 associates intra-molecularly to form higher order complexes, which may be needed for endoproteolytic cleavage and/or γ-secretase-associated activity.

【 授权许可】

Unknown