Homodimerization protects the amyloid precursor protein C99 fragment from cleavage by γ-secretase
Biochemistry. 2015 Oct 13;54(40):6149-52.
| Authors/Editors: |
Winkler E Julius A Steiner H Langosch D |
|---|---|
| Type of Publication: | Journal Article |
The amyloid precursor protein (APP) is a single-span integral membrane protein whose C-terminal fragment C99 is cleaved within the transmembrane helix by γ-secretase. Cleavage produces various Aβ peptides that are linked to the etiology of Alzheimer's disease. The transmembrane helix is known to homodimerize in a sequence-specific manner, and considerable controversy about whether the homodimeric form of C99 is cleaved by γ-secretase exists. Here, we generated various covalent C99 homodimers via cross-linking at engineered cysteine residues. None of the homodimers was cleaved in vitro by purified γ-secretase, strongly suggesting that homodimerization protects C99 from cleavage.
