PMID: 30630874

 

    Legend: Gene, Sites

Title : Recognition of the amyloid precursor protein by human γ-secretase

Abstract :

1. Cleavage of amyloid precursor protein ( APP ) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD)
2. We report an atomic structure of human γ-secretase in complex with a transmembrane ( TM) APP fragment at 2.6-angstrom resolution
3. The TM helix of APP closely interacts with five surrounding TMs of PS1 (the catalytic subunit of γ-secretase)
4. A hybrid β sheet, which is formed by a β strand from APP and two β strands from PS1 , guides γ-secretase to the scissile peptide bond of APP between its TM and β strand
5. Residues at the interface between PS1 and APP are heavily targeted by recurring mutations from AD patients
6. This structure, together with that of γ-secretase bound to Notch, reveal contrasting features of substrate binding, which may be applied toward the design of substrate-specific inhibitors

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
PS1	5663	3,4,5
amyloid precursor protein	351	0,1