Domain organization of long signal peptides of single-pass integral membrane proteins reveals multiple functional capacity

Targeting signals direct proteins to their extra- or intracellular destination such as the plasma membrane or cellular organelles. Here we investigated the structure and function of exceptionally long signal peptides enc
Targeting signals direct proteins to their extra- or intracellular destination such as the plasma membrane or cellular organelles. Here we investigated the structure and function of exceptionally long signal peptides encompassing at least 40 amino acid residues. We discovered a two-domain organization ("NtraC model") in many long signals from vertebrate precursor proteins. Accordingly, long signal peptides may contain an N-terminal domain (N-domain) and a C-terminal domain (C-domain) with different signal or targeting capabilities, separable by a presumably turn-rich transition area (tra). Individual domain functions were probed by cellular targeting experiments with fusion proteins containing parts of the long signal peptide of human membrane protein shrew-1 and secreted alkaline phosphatase as a reporter protein. As predicted, the N-domain of the fusion protein alone was shown to act as a mitochondrial targeting signal, whereas the C-domain alone functions as an export signal. Selective disruption of the transition area in the signal peptide impairs the export efficiency of the reporter protein. Altogether, the results of cellular targeting studies provide a proof-of-principle for our NtraC model and highlight the particular functional importance of the predicted transition area, which critically affects the rate of protein export. In conclusion, the NtraC approach enables the systematic detection and prediction of cryptic targeting signals present in one coherent sequence, and provides a structurally motivated basis for decoding the functional complexity of long protein targeting signals.
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Metadaten
Author:Jan Alexander Hiß, Eduard Resch, Alexander Schreiner, Michael Meissner, Anna Starzinski-Powitz, Gisbert Schneider
URN:urn:nbn:de:hebis:30-60257
DOI:http://dx.doi.org/10.1371/journal.pone.0002767
ISSN:1932-6203
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=18648515
Parent Title (English):PLoS one
Publisher:Public Library of Science
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2008/07/23
Date of first Publication:2008/07/23
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2008/11/12
Volume:3
Issue:(7): e2767
Pagenumber:8
First Page:1
Last Page:8
Note:
Copyright:  2008 Hiss et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS PPN:208598073
Institutes:Biowissenschaften
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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