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-Structure paper
Title | Recognition of the amyloid precursor protein by human γ-secretase. |
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Journal, issue, pages | Science, Vol. 363, Issue 6428, Year 2019 |
Publish date | Feb 15, 2019 |
Authors | Rui Zhou / Guanghui Yang / Xuefei Guo / Qiang Zhou / Jianlin Lei / Yigong Shi / |
PubMed Abstract | Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD). We report an atomic structure of human γ-secretase in complex with a ...Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD). We report an atomic structure of human γ-secretase in complex with a transmembrane (TM) APP fragment at 2.6-angstrom resolution. The TM helix of APP closely interacts with five surrounding TMs of PS1 (the catalytic subunit of γ-secretase). 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. Residues at the interface between PS1 and APP are heavily targeted by recurring mutations from AD patients. 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. |
External links | Science / PubMed:30630874 |
Methods | EM (single particle) |
Resolution | 2.6 Å |
Structure data | |
Chemicals | ChemComp-NAG: ChemComp-PC1: ChemComp-CLR: |
Source |
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Keywords | MEMBRANE PROTEIN / Complex |