Sampling the conformational space of the catalytic subunit of human γ-secretase
MRC Laboratory of Molecular Biology · Center for Life Sciences · +1 more institution
Abstract
Human γ-secretase is an intra-membrane protease that cleaves many different substrates. Aberrant cleavage of Notch is implicated in cancer, while abnormalities in cutting amyloid precursor protein lead to Alzheimer's disease. Our previous cryo-EM structure of γ-secretase revealed considerable disorder in its catalytic subunit presenilin. Here, we describe an image classification procedure that characterizes molecular plasticity at the secondary structure level, and apply this method to identify three distinct conformations in our previous sample. In one of these conformations, an additional transmembrane helix is visible that cannot be attributed to the known components of γ-secretase. In addition, we present…
Citation impact
- FWCI
- 40.79
- Percentile
- 100%
- References
- 54
Authors
5Topics & keywords
- Presenilin
- Transmembrane domain
- Transmembrane protein
- Protein subunit
- Amyloid precursor protein secretase
- Cleavage (geology)
- Helix (gastropod)
- Amyloid precursor protein