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Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18629-18637. doi: 10.1073/pnas.1821060116. Epub 2019 Aug 26.

The expanded specificity and physiological role of a widespread N-degron recognin.

Author information

1
Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536.
2
Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536; eduardo.groisman@yale.edu.
3
Yale Microbial Sciences Institute, West Haven, CT 06516.

Abstract

All cells use proteases to maintain protein homeostasis. The proteolytic systems known as the N-degron pathways recognize signals at the N terminus of proteins and bring about the degradation of these proteins. The ClpS protein enforces the N-degron pathway in bacteria and bacteria-derived organelles by targeting proteins harboring leucine, phenylalanine, tryptophan, or tyrosine at the N terminus for degradation by the protease ClpAP. We now report that ClpS binds, and ClpSAP degrades, proteins still harboring the N-terminal methionine. We determine that ClpS recognizes a type of degron in intact proteins based on the identity of the fourth amino acid from the N terminus, showing a strong preference for large hydrophobic amino acids. We uncover natural ClpS substrates in the bacterium Salmonella enterica, including SpoT, the essential synthase/hydrolase of the alarmone (p)ppGpp. Our findings expand both the specificity and physiological role of the widespread N-degron recognin ClpS.

KEYWORDS:

ClpAP; ClpS; SpoT; proteolysis

PMID:
31451664
PMCID:
PMC6744884
[Available on 2020-02-26]
DOI:
10.1073/pnas.1821060116

Conflict of interest statement

The authors declare no conflict of interest.

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