eprintid: 8473 rev_number: 8 eprint_status: archive userid: 1 dir: disk0/00/00/84/73 datestamp: 2008-06-17 15:16:29 lastmod: 2014-08-18 09:50:20 status_changed: 2012-08-14 15:25:35 type: article metadata_visibility: show creators_name: Haeuptle, Marie-Theres creators_name: Flint, Nicholas creators_name: Gough, Nicholas M. creators_name: Dobberstein, Bernhard title: A Tripartite Structure of the Signals that Determine Protein Insertion into the Endoplasmic Reticulum Membrane ispublished: pub subjects: ddc-570 divisions: i-706000 abstract: Multilineage colony stimulating factor is a secretory protein with a cleavable signal sequence that is unusually long and hydrophobic. Using molecular cloning techniques we exchanged sequences NH2- or COOH-terminally flanking the hydrophobic signal sequence. Such modified fusion proteins still inserted into the membrane but their signal sequence was not cleaved. Instead the proteins were now anchored in the membrane by the formerly cleaved signal sequence (signal-anchor sequence). They exposed the NH2 terminus on the exoplasmic and the COOH terminus on the cytoplasmic side of the membrane. We conclude from our results that hydrophilic sequences flanking the hydrophobic core of a signal sequence can determine cleavage by signal peptidase and insertion into the membrane. It appears that negatively charged amino acid residues close to the NH2 terminal side of the hydrophobic segment are compatible with translocation of this segment across the membrane. A tripartite structure is proposed for signal-anchor sequences: a hydrophobic core region that mediates targeting to and insertion into the ER membrane and flanking hydrophilic segments that determine the orientation of the protein in the membrane. abstract_translated_lang: eng date: 1989 date_type: published id_scheme: DOI id_number: 10.11588/heidok.00008473 schriftenreihe_cluster_id: sr-2 schriftenreihe_order: 044 ppn_swb: 1352624478 own_urn: urn:nbn:de:bsz:16-opus-84737 language: eng bibsort: HAEUPTLEMAATRIPARTIT1989 full_text_status: public publication: The Journal of Cell Biology volume: 108 pagerange: 1227-1236 citation: Haeuptle, Marie-Theres ; Flint, Nicholas ; Gough, Nicholas M. ; Dobberstein, Bernhard (1989) A Tripartite Structure of the Signals that Determine Protein Insertion into the Endoplasmic Reticulum Membrane. The Journal of Cell Biology, 108. pp. 1227-1236. document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/8473/1/Haeuptle_1989_JCB.pdf