title: Signal peptidase can cleave inside a polytopic membrane protein.
abstract: The signal peptides of most proteins targeted to the endoplasmic reticulum are specifically cleaved by signal peptidase. Although potential cleavage sites occur frequently in polytopic proteins after membrane-spanning segments, processing is restricted to the first hydrophobic domain, suggesting that signal peptidase might not have access to subsequently translocated, internal domains. To test this hypothesis, we replaced the third transmembrane segment of an artificial threefold membrane-spanning protein by a sequence which is normally an amino-terminal signal. Upon in vitro translation and insertion into microsomes, efficient cleavage at this sequence was observed, thus demonstrating the ability of signal peptidase to cleave within polytopic membrane proteins.
authors.affiliation: Department of Biochemistry, Biocenter, University of Basel; Switzerland
authors.forename: J P
authors.initials: JP
authors.lastname: Beltzer
authors.forename: H P
authors.initials: HP
authors.lastname: Wessels
authors.forename: M
authors.initials: M
authors.lastname: Spiess
mesh_terms: D037263:Asialoglycoprotein Receptor; D002474:Cell-Free System; D010450:Endopeptidases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000502:physiology; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases; D013329:Structure-Activity Relationship
chemical_list: D037263:Asialoglycoprotein Receptor; D006389:Hemagglutinins, Viral; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase