Journal
NATURE
Volume 459, Issue 7245, Pages 371-378Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature08146
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Funding
- Israel Science Foundation
- Yale-Weizmann Collaborative Program
- Kimmelman Center for Macromolecular Assemblies
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Intramembrane proteolysis is increasingly seen as a regulatory step in a range of diverse processes, including development, organelle shaping, metabolism, pathogenicity and degenerative disease. Initial scepticism over the existence of intramembrane proteases was soon replaced by intense exploration of their catalytic mechanisms, substrate specificities, regulation and structures. Crystal structures of metal-dependent and serine intramembrane proteases have revealed active sites embedded in the plane of the membrane but accessible by water, a requirement for hydrolytic reactions. Efforts to understand how these membrane-bound proteases carry out their reactions have started to yield results.
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