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J Biol Chem. 2017 Dec 29;292(52):21383-21396. doi: 10.1074/jbc.M117.788067. Epub 2017 Oct 30.

The Sec61/SecY complex is inherently deficient in translocating intrinsically disordered proteins.

Author information

1
From the Departments of Biochemistry of Neurodegenerative Diseases and.
2
the Institute of Biochemistry and Molecular Biology, Faculty of Medicine, Albert-Ludwigs-University Freiburg, D-79104 Freiburg im Breisgau, Germany.
3
the Department of Medical Biochemistry and Molecular Biology, Saarland University, D-66421 Homburg, Germany, and.
4
the Research Group Proteinopathies/Neurodegenerative Diseases, Centre for Biological Threats and Special Pathogens, Robert Koch-Institut, D-13353 Berlin, Germany.
5
Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, D-44801 Bochum, Germany.
6
From the Departments of Biochemistry of Neurodegenerative Diseases and Joerg.Tatzelt@rub.de.

Abstract

About one-quarter to nearly one-third of the proteins synthesized in the cytosol of eukaryotic cells are integrated into the plasma membrane or are secreted. Translocation of secretory proteins into the lumen of the endoplasmic reticulum or the periplasm of bacteria is mediated by a highly conserved heterotrimeric membrane protein complex denoted Sec61 in eukaryotes and SecYEG in bacteria. To evaluate a possible modulation of the translocation efficiency by secondary structures of the nascent peptide chain, we performed a comparative analysis in bacteria, yeast, and mammalian cells. Strikingly, neither the bacterial SecY nor the eukaryotic Sec61 translocon was able to efficiently transport proteins entirely composed of intrinsically disordered domains (IDDs) or β-strands. However, translocation could be restored by α-helical domains in a position- and organism-dependent manner. In bacteria, we found that the α-helical domains have to precede the IDD or β-strands, whereas in mammalian cells, C-terminally located α-helical domains are sufficient to promote translocation. Our study reveals an evolutionarily conserved deficiency of the Sec61/SecY complex to translocate IDDs and β-strands in the absence of α-helical domains. Moreover, our results may suggest that adaptive pathways co-evolved with the expansion of IDDs in the proteome of eukaryotic cells to increase the transport capacity of the Sec61 translocon.

KEYWORDS:

ER import; Sec61; SecY; endoplasmic reticulum (ER); intrinsically disordered protein; prion; protein secretion; protein translocation

PMID:
29084847
PMCID:
PMC5766967
[Available on 2018-12-29]
DOI:
10.1074/jbc.M117.788067
[Indexed for MEDLINE]

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