title: Structure of the integral membrane protein CAAX protease Ste24p.
abstract: Posttranslational lipidation provides critical modulation of the functions of some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X is any residue). Isoprenylation is followed by cleavage of the AAX amino acid residues and, in some cases, by additional proteolytic cuts. We determined the crystal structure of the CAAX protease Ste24p, a zinc metalloprotease catalyzing two proteolytic steps in the maturation of yeast mating pheromone a-factor. The Ste24p core structure is a ring of seven transmembrane helices enclosing a voluminous cavity containing the active site and substrate-binding groove. The cavity is accessible to the external milieu by means of gaps between splayed transmembrane helices. We hypothesize that cleavage proceeds by means of a processive mechanism of substrate insertion, translocation, and ejection.
authors.affiliation: Membrane Protein Structural Biology Consortium, USA.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Pryor
authors.forename: Peter S
authors.initials: PS
authors.lastname: Horanyi
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Clark
authors.forename: Nadia
authors.initials: N
authors.lastname: Fedoriw
authors.forename: Sara M
authors.initials: SM
authors.lastname: Connelly
authors.forename: Mary
authors.initials: M
authors.lastname: Koszelak-Rosenblum
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
authors.forename: Michael G
authors.initials: MG
authors.lastname: Malkowski
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wiener
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dumont
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D002462:Cell Membrane / Q000201:enzymology*; D018360:Crystallography, X-Ray; D008565:Membrane Proteins / Q000737:chemistry*; D008666:Metalloendopeptidases / Q000737:chemistry*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D008666:Metalloendopeptidases; C491251:STE24 protein, S cerevisiae
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