title: The N-terminal motif of PMP70 suppresses cotranslational targeting to the endoplasmic reticulum.
abstract: Many membrane proteins possessing hydrophobic transmembrane (TM) segments are cotranslationally integrated into the endoplasmic reticulum (ER) membrane. Various peroxisomal and mitochondrial membrane proteins escape the ER-targeting mechanism and are targeted to their destinations. Here, we discovered a short segment in the 70-kDa peroxisomal membrane protein (PMP70) that suppresses ER targeting. The first TM segment has an intrinsic signal function that targets the nascent chain to the ER. The ER targeting was suppressed by a short N-terminal sequence of nine residues that is 80 residues upstream of the TM segment. Among the nine residues, Ser(5) is indispensable. The short segment also suppressed the signal peptide function of an authentic secretory protein. This function of the short segment was suppressed by the recombinant motif-GST fusion protein. The 50-kDa and 20-kDa proteins were crosslinked with the motif. The PMP70 molecule with the Ser5Ala point mutation predominantly localized to the ER. We propose the concept of an ER-targeting suppressor that suppresses the ER-targeting mechanism via a binding factor.
authors.affiliation: Graduate School of Life Science, University of Hyogo, Ako, Hyogo 678-1297, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Sakaue
authors.affiliation: Graduate School of Life Science, University of Hyogo, Ako, Hyogo 678-1297, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Iwashita
authors.affiliation: Graduate School of Life Science, University of Hyogo, Ako, Hyogo 678-1297, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Graduate School of Life Science, University of Hyogo, Ako, Hyogo 678-1297, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kida
authors.affiliation: Graduate School of Life Science, University of Hyogo, Ako, Hyogo 678-1297, Japan sakag@sci.u-hyogo.ac.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Sakaguchi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D000072417:Protein Domains; D021381:Protein Transport / Q000502:physiology
chemical_list: C063305:ABCD3 protein, human; D018528:ATP-Binding Cassette Transporters
keywords: endoplasmic reticulum; membrane proteins; peroxisomes; protein sorting; signal sequence