Substrate-specific regulation of the ribosome– translocon junction by N-terminal signal sequences

D. Thomas Rutkowski; Vishwanath R Lingappa; Ramanujan S Hegde

doi:10.1073/pnas.141125098

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Substrate-specific regulation of the ribosome– translocon junction by N-terminal signal sequences

Journal article

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Substrate-specific regulation of the ribosome– translocon junction by N-terminal signal sequences

D. Thomas Rutkowski, Vishwanath R Lingappa and Ramanujan S Hegde

Proceedings of the National Academy of Sciences - PNAS, Vol.98(14), pp.7823-7828

07/03/2001

DOI: 10.1073/pnas.141125098

PMCID: PMC35426

PMID: 11416167

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Abstract

Amino-terminal signal sequences target nascent secretory and membrane proteins to the endoplasmic reticulum for translocation. Subsequent interactions between the signal sequence and components of the translocation machinery at the endoplasmic reticulum are thought to be important for the productive engagement of the translocon by the ribosome-nascent chain complex. However, it is not clear whether all signal sequences carry out these posttargeting steps identically, or if there are differences in the interactions directed by one signal sequence versus another. In this study, we find substantial differences in the ability of signal sequences from different substrates to mediate closure of the ribosome–translocon junction early in translocation. We also show that these differences in some cases necessitate functional coordination between the signal sequence and mature domain for faithful translocation. Accordingly, the translocation of some proteins is sensitive to replacement of their signal sequences. In a particularly dramatic example, the topology of the prion protein was found to depend highly on the choice of signal sequence used to direct its translocation. Taken together, our results reveal an unanticipated degree of substrate-specific functionality encoded in N-terminal signal sequences.

Biological Sciences

Details

Title: Subtitle: Substrate-specific regulation of the ribosome– translocon junction by N-terminal signal sequences
Creators: D. Thomas Rutkowski - Departments of
Vishwanath R Lingappa - Departments of
Ramanujan S Hegde - Departments of
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.98(14), pp.7823-7828
DOI: 10.1073/pnas.141125098
PMID: 11416167
PMCID: PMC35426
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 07/03/2001
Academic Unit: Anatomy and Cell Biology; Internal Medicine
Record Identifier: 9984094546302771

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