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PMID: 12853479 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular mechanism of signal sequence orientation in the endoplasmic reticulum.

The EMBO journal ·Vol. 22 ·No. 14 ·2003-07-15 ·Pages 3645-53

Goder V, Spiess M

Abstract

We have analyzed in vivo how model signal sequences are inserted and oriented in the membrane during cotranslational integration into the endoplasmic reticulum. The results are incompatible with the current models of retention of positive flanking charges or loop insertion of the polypeptide into the translocon. Instead they indicate that these N-terminal signals initially insert head-on with a cytoplasmic C-terminus before they invert their orientation to translocate the C-terminus. The rate of inversion increases with more positive N-terminal charge and is reduced with increasing hydrophobicity of the signal. Inversion may proceed for up to approximately 50 s, when it is terminated by a signal-independent process. These findings provide a mechanism for the topogenic effects of flanking charges as well as of signal hydrophobicity.

MeSH Terms
Animals COS Cells Chlorocebus aethiops Endoplasmic Reticulum/metabolism Glycosylation Hydrophobic and Hydrophilic Interactions Intracellular Membranes/metabolism Kinetics Membrane Proteins/chemistry,genetics,metabolism Models, Biological Molecular Sequence Data Protein Conformation Protein Processing, Post-Translational Protein Sorting Signals/genetics Protein Structure, Tertiary Recombinant Fusion Proteins/chemistry,metabolism Static Electricity Time Factors
Chemicals
Membrane Proteins Protein Sorting Signals Recombinant Fusion Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Goder Veit
Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Spiess Martin
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg361
Published
2003-07-15
Pages
3645-53
Language
English
Region
England
NLM ID
8208664
PMCID
PMC165631
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg361 PMC Full Text View journal details
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