N-terminal signal peptides direct secretory proteins into the ER (endoplasmic reticulum) of eukaryotes or the periplasmic space of prokaryotes. A hydrophobic core (h-region) is important for signal sequence function; however, the mechanism of h-region action is not resolved. To gain new insight into signal sequences, bioinformatic analysis of h-regions from humans, Saccharomyces cerevisiae, Trypanosoma brucei and Escherichia coli was performed. Each species contains a unique set of peptide motifs (h-motifs) characterized by identity components (i.e. sequence of conserved amino acids) joined by spacers. Human h-motifs have four identity components, whereas those from the other species utilize three identity components. Example of h-motifs are human Hs3 {L-x(2)-[AGILPV]-L-x(0,2)-L}, S. cerevisiae Sc1 [L-x(0,2)-S-x(0,3)-A], T. brucei Tb2 {L-x(1,2)-L-[AILV]} and E. coli Ec1 [A-x(0,2)-L-x(0,3)-A]. The physiological relevance of h-motifs was tested with a T. brucei microsomal system for translocation of a VSG (variant surface glycoprotein)-117 signal peptide. Disruption of h-motifs by scrambling of sequences in h-regions produced defective signal peptides, although the hydrophobicity of the peptide was not altered. We conclude that: (i) h-regions harbour h-motifs, and are not random hydrophobic amino acids; (ii) h-regions from different species contain unique sets of h-motifs; and (iii) h-motifs contribute to the biological activity of ER signal peptides. h-Regions are ‘scaffolds’ in which functional h-motifs are embedded. A hypothetical model for h-motif interactions with a Sec61p protein translocon is presented.
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Research Article|
February 09 2010
Discovery of functional motifs in h-regions of trypanosome signal sequences
Josh Duffy;
Josh Duffy
1
1Department of Cellular Biology, 724 Biological Sciences Building, University of Georgia, Athens, GA 30602, U.S.A.
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Kojo Mensa-Wilmot
Kojo Mensa-Wilmot
3
1Department of Cellular Biology, 724 Biological Sciences Building, University of Georgia, Athens, GA 30602, U.S.A.
3To whom correspondence should be addressed (email mensawil@uga.edu).
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Publisher: Portland Press Ltd
Received:
August 14 2009
Revision Received:
December 15 2009
Accepted:
December 18 2009
Accepted Manuscript online:
December 18 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 426 (2): 135–145.
Article history
Received:
August 14 2009
Revision Received:
December 15 2009
Accepted:
December 18 2009
Accepted Manuscript online:
December 18 2009
Citation
Josh Duffy, Bhargavi Patham, Kojo Mensa-Wilmot; Discovery of functional motifs in h-regions of trypanosome signal sequences. Biochem J 1 March 2010; 426 (2): 135–145. doi: https://doi.org/10.1042/BJ20091277
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