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Orientation of Internal Signal-Anchor Sequences at the Sec61 Translocon

Kocik, Lucyna and Junne, Tina and Spiess, Martin. (2012) Orientation of Internal Signal-Anchor Sequences at the Sec61 Translocon. Journal of molecular biology, Vol. 424, H. 5. pp. 368-378.

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Official URL: http://edoc.unibas.ch/dok/A6043822

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Abstract

Translocation and insertion of secretory and membrane proteins at the endoplasmic reticulum are mediated by the Sec61 translocon. Evidence from in vivo as well as in vitro experiments indicates that N-terminal signal-anchor sequences initially insert N-first before they invert their orientation to translocate the C-terminus. Inversion is driven by flanking charges according to the positive-inside rule and inhibited by increased signal hydrophobicity. Here, we show that upon extending the N-terminal hydrophilic domain preceding the signal core to more than ~20 residues, the insertion behavior changes. Apparent signal inversion and the effect of hydrophobicity are largely lost, suggesting that N-first insertion is limited to N-terminal signal anchors. Extended N-domains sterically hinder N-translocation in a length-dependent manner also for reverse signal anchors with inverted flanking charges. The results indicate a mechanistic difference in the insertion process of N-terminal and internal signal sequences.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Spiess)
UniBasel Contributors:Spiess, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0022-2836
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:39

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