4cad

Mechanism of farnesylated CAAX protein processing by the integral membrane protease Rce1Mechanism of farnesylated CAAX protein processing by the integral membrane protease Rce1

Structural highlights 4cad is a 12 chain structure with sequence from Methanococcus maripaludis 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 2.5Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RCE1_METMP Endopeptidase which proteolytically removes the C-terminal three residues of farnesylated peptides containing the CAAX motif where C is cysteine, A is an aliphatic amino acid and X is any amino acid. Cleaves the CAAX motif C-terminal to both P1 and P1' positions. Hydrolysis depends on a farnesylated cysteine residue and no activity is shown towards geranylgeranylated peptides. Publication Abstract from PubMed CAAX proteins have essential roles in multiple signalling pathways, controlling processes such as proliferation, differentiation and carcinogenesis. The approximately 120 mammalian CAAX proteins function at cellular membranes and include the Ras superfamily of small GTPases, nuclear lamins, the gamma-subunit of heterotrimeric GTPases, and several protein kinases and phosphatases. The proper localization of CAAX proteins to cell membranes is orchestrated by a series of post-translational modifications of the carboxy-terminal CAAX motifs (where C is cysteine, A is an aliphatic amino acid and X is any amino acid). These reactions involve prenylation of the cysteine residue, cleavage at the AAX tripeptide and methylation of the carboxyl-prenylated cysteine residue. The major CAAX protease activity is mediated by Rce1 (Ras and a-factor converting enzyme 1), an intramembrane protease (IMP) of the endoplasmic reticulum. Information on the architecture and proteolytic mechanism of Rce1 has been lacking. Here we report the crystal structure of a Methanococcus maripaludis homologue of Rce1, whose endopeptidase specificity for farnesylated peptides mimics that of eukaryotic Rce1. Its structure, comprising eight transmembrane alpha-helices, and catalytic site are distinct from those of other IMPs. The catalytic residues are located approximately 10 A into the membrane and are exposed to the cytoplasm and membrane through a conical cavity that accommodates the prenylated CAAX substrate. We propose that the farnesyl lipid binds to a site at the opening of two transmembrane alpha-helices, which results in the scissile bond being positioned adjacent to a glutamate-activated nucleophilic water molecule. This study suggests that Rce1 is the founding member of a novel IMP family, the glutamate IMPs. Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1.,Manolaridis I, Kulkarni K, Dodd RB, Ogasawara S, Zhang Z, Bineva G, O'Reilly N, Hanrahan SJ, Thompson AJ, Cronin N, Iwata S, Barford D Nature. 2013 Dec 1. doi: 10.1038/nature12754. PMID:24291792 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures 3D structures of non-human antibody

spinqualitylabelsall models 4cad, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image