CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides.
Science
; 357(6349): 414-417, 2017 07 28.
Article
in En
| MEDLINE
| ID: mdl-28751611
ABSTRACT
Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p-accessible lysines, CAT-tailing enabled degradation by exposing lysines sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that expands the range of RQC-degradable substrates.
Full text:
1
Database:
MEDLINE
Main subject:
Peptides
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Ribosomes
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Saccharomyces cerevisiae
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Saccharomyces cerevisiae Proteins
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Ubiquitin-Protein Ligases
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Proteolysis
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Transcription Elongation, Genetic
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Proteostasis
Language:
En
Journal:
Science
Year:
2017
Type:
Article
Affiliation country:
United States