7w71

Crystal structure of the PDZ-C domain of E. coli RseP in complex with 12C7 Fab

spinqualitylabelsall models 7w71, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7w71 is a 6 chain structure with sequence from Escherichia coli and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RSEP_ECOLI A site-2 regulated intramembrane protease (S2P) that cleaves the peptide bond between 'Ala-108' and 'Cys-109' in the transmembrane region of RseA. Part of a regulated intramembrane proteolysis (RIP) cascade. Acts on DegS-cleaved RseA to release the cytoplasmic domain of RseA, residue "Val-148" of RseA may be required for this. This provides the cell with sigma-E (RpoE) activity through the proteolysis of RseA. Can also cleave sequences in transmembrane regions of other proteins (such as LacY) as well as liberated signal peptides of beta-lactamase, OmpF, LivK, SecM, PhoA, LivJ, OmpC, Lpp and TorA, probably within the membrane. Publication Abstract from PubMed Site-2 proteases are a conserved family of intramembrane proteases that cleave transmembrane substrates to regulate signal transduction and maintain proteostasis. Here, we elucidated crystal structures of inhibitor-bound forms of bacterial site-2 proteases including Escherichia coli RseP. Structure-based chemical modification and cross-linking experiments indicated that the RseP domains surrounding the active center undergo conformational changes to expose the substrate-binding site, suggesting that RseP has a gating mechanism to regulate substrate entry. Furthermore, mutational analysis suggests that a conserved electrostatic linkage between the transmembrane and peripheral membrane-associated domains mediates the conformational changes. In vivo cleavage assays also support that the substrate transmembrane helix is unwound by strand addition to the intramembrane beta sheet of RseP and is clamped by a conserved asparagine residue at the active center for efficient cleavage. This mechanism underlying the substrate binding, i.e., unwinding and clamping, appears common across distinct families of intramembrane proteases that cleave transmembrane segments. Mechanistic insights into intramembrane proteolysis by E. coli site-2 protease homolog RseP.,Imaizumi Y, Takanuki K, Miyake T, Takemoto M, Hirata K, Hirose M, Oi R, Kobayashi T, Miyoshi K, Aruga R, Yokoyama T, Katagiri S, Matsuura H, Iwasaki K, Kato T, Kaneko MK, Kato Y, Tajiri M, Akashi S, Nureki O, Hizukuri Y, Akiyama Y, Nogi T Sci Adv. 2022 Aug 26;8(34):eabp9011. doi: 10.1126/sciadv.abp9011. Epub 2022 Aug, 24. PMID:36001659 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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