Sci. STKE, 11 December 2007
Structural Biology Making the Right Cut
Science, AAAS, Washington, DC 20005, USA
Regulated intramembrane proteolysis (RIP) represents an important signaling mechanism that is conserved from bacteria to humans. A notable example of RIP is the activation by cleavage of the transcription factor sterol regulatory element-binding protein by site-2 protease (S2P), a key event in regulating cellular cholesterol levels. Feng et al. now present the crystal structure of the transmembrane core of an archaebacterial S2P metalloprotease, which provides insight into how S2P functions. The structure shows the mechanism of cleavage at an active site, containing a catalytic zinc ion that is embedded deep in the membrane. Two conformations observed in the crystals suggest that a helical gating mechanism controls substrate access.
Citation: V. Vinson, Making the Right Cut. Sci. STKE 2007, tw453 (2007).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882