期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 37, 页码 18629-18637出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1821060116
关键词
ClpAP; ClpS; proteolysis; SpoT
资金
- NIH [AI49561]
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.
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