Integration of transmembrane domains is regulated by their downstream sequences

Junne, Tina and Spiess, Martin. (2017) Integration of transmembrane domains is regulated by their downstream sequences. Journal of Cell Science, 130. pp. 372-381.

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Official URL: http://edoc.unibas.ch/53022/

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The Sec61 translocon catalyzes translocation of proteins into the endoplasmic reticulum and the lateral integration of transmembrane segments into the lipid bilayer. Integration is mediated by the hydrophobicity of a polypeptide segment consistent with thermodynamic equilibration between the translocon and the lipid membrane. Integration efficiency of a generic series of increasingly hydrophobic sequences (H-segments) was found to diverge significantly in different reporter constructs as a function of the ∼100 residues carboxyterminal of the H-segments. The hydrophobicity threshold of integration was considerably lowered by insertion of generic ∼20-residue peptides either made of flexible glycine-serine repeats, containing multiple negative charges, or consisting of an oligo-proline stretch. A highly flexible, 100-residue glycine-serine stretch maximally enhanced this effect. The apparent free energy of integration was found to be changed by more than 3 kcal/mol with the downstream sequences tested. The C-terminal sequences could also be shown to affect integration of natural mildly hydrophobic sequences. The results suggest that the conformation of the nascent polypeptide in the protected cavity between ribosome and translocon significantly influences the release of the H-segment into the bilayer.
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
Publisher:Company of Biologists
Note:Publication type according to Uni Basel Research Database: Journal article
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edoc DOI:
Last Modified:23 Feb 2018 14:32
Deposited On:12 Oct 2017 06:50

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