Structure of human γ-secretase is finally obtained! Group leaded by Sjors Scheres from LMB in Cambridge used cryo-EM technique to reveal it at resolution of 4.5 Å! They published their findings in Nature.
The discovery is of great importance as mutations in human γ-secretase have been shown to play crucial role in Alzheimer’s disease. Mutated enzyme hydrolyzes amyloid precursor protein (APP). Product of this hydrolysis forms plaques in our brain and those plaques were linked to Alzheimer’s disease.
Thanks to discovery, researchers will be able to work on possible inhibitors that can make secretase stop hydrolyzing APP. Previously, unsuccessful attempts were made in labs around the world to obtain structure by typical methods like x-ray crystallography and NMR technique.
Cryo-EM is a wonderful technique that allows us to see molecular machines in their native environment! We don’t have to stain them or try to make wonderfull crystals of them. Although cryo-EM is young and still developing method, due to those advantages, it is growing in popularity amongst structural biologists.
Here is short and brilliant introduction to cryo-EM:
And if you wanna get more experience visit those pages:
- Leschziner Lab’s Tutorials Wiki, page made by group from Harvard University, covers physics and mathematics behind cryo-EM and data analysis.
- Dr. Sjors Scheres make available his video lectures on cryo-EM for free – they can be downloaded here in high resolution.
- Nice review (although quite advanced) on structural analysis by electron microscopy from Chemical Reviews.