Oligomerization of human presenilin-1 fragments.
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 gamma-secretase-associated activity.
Hébert
Sébastien S
SS
Molecular and Human Genetics Unit, CHUQ-Pavillon St-François d'Assise, 10 rue de l'Espinay, Quebec, QC, Canada G1L 3L5.
Godin
Chantal
C
Lévesque
Georges
G
D019281:Dimerization; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1; D017434:Protein Structure, Tertiary / Q000502:physiology; D013329:Structure-Activity Relationship; D020798:Two-Hybrid System Techniques
D046911:Macromolecular Substances; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1