Structural highlights
Function
[Y392_METJA] A site-2 regulated intramembrane protease (S2P), its endogenous substrate is unknown. Regulated intramembrane proteolysis (RIP) occurs when an extracytoplasmic signal triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. A membrane-spanning regulatory substrate protein is first cut extracytoplasmically (site-1 protease, S1P), then within the membrane itself (site-2 protease, S2P, this enzyme), while cytoplasmic proteases finish degrading the regulatory protein, liberating the effector protein. Possible signals, S1P and substrates are unknown in this organism.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Regulated intramembrane proteolysis by members of the site-2 protease (S2P) family is an important signaling mechanism conserved from bacteria to humans. Here we report the crystal structure of the transmembrane core domain of an S2P metalloprotease from Methanocaldococcus jannaschii. The protease consists of six transmembrane segments, with the catalytic zinc atom coordinated by two histidine residues and one aspartate residue approximately 14 angstroms into the lipid membrane surface. The protease exhibits two distinct conformations in the crystals. In the closed conformation, the active site is surrounded by transmembrane helices and is impermeable to substrate peptide; water molecules gain access to zinc through a polar, central channel that opens to the cytosolic side. In the open conformation, transmembrane helices alpha1 and alpha6 separate from each other by 10 to 12 angstroms, exposing the active site to substrate entry. The structure reveals how zinc embedded in an integral membrane protein can catalyze peptide cleavage.
Structure of a site-2 protease family intramembrane metalloprotease.,Feng L, Yan H, Wu Z, Yan N, Wang Z, Jeffrey PD, Shi Y Science. 2007 Dec 7;318(5856):1608-12. PMID:18063795[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Feng L, Yan H, Wu Z, Yan N, Wang Z, Jeffrey PD, Shi Y. Structure of a site-2 protease family intramembrane metalloprotease. Science. 2007 Dec 7;318(5856):1608-12. PMID:18063795 doi:318/5856/1608
