期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 9, 页码 3078-3083出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0511224103
关键词
proteolysis; ClpAP; ClpS; Aat; bacterial protein transferase
资金
- NIDDK NIH HHS [R56 DK039520, R37 DK039520, R01 DK039520, DK39520] Funding Source: Medline
- NIGMS NIH HHS [R01 GM031530, GM31530] Funding Source: Medline
The Wend rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Primary destabilizing N-terminal residues (Nd-p) are recognized directly by the targeting machinery. The recognition of secondary destabilizing N-terminal residues (Nd-s) is preceded by conjugation of an Nd-p residue to Nd-5 of a polypeptide substrate. In eukaryotes, ATE1-encoded arginyl-transferases (R-D,R-E,R- C*-transferases) conjugate Arg (R), an Nd-p residue, to Nd-5 residues Asp (D), Glu (E), or oxidized Cys residue (C*). Ubiquitin ligases recognize the N-terminal Arg of a substrate and target the (ubiquitylated) substrate to the proteasome. In prokaryotes such as Escherichia coli, Nd-p residues Leu (L) or Phe (F) are conjugated, by the aat-encoded Leu/Phe-transferase (L/F-K,F-R-transferase), to N-terminal Arg or Lys, which are Nds in prokaryotes but Nd-p in eukaryotes. In prokaryotes, substrates bearing the Nd-p residues Leu, Phe, Trp, or Tyr are degraded by the proteasome-like ClpAP protease. Despite enzymological similarities between eukaryotic R-D,R-E,R-C*-transferases and prokaryotic L/F-K,F-R-transferases, there is no significant sequelogy (sequence similarity) between them. We identified an aminoacyl-transferase, termed Bpt, in the human pathogen Vibrio vulnificus. Although it is a sequelog of eukaryotic R-D,R-E,R-C*-transferases, this prokaryotic transferase exhibits a hybrid specificity, conjugating Nd-p Leu to Nd-5 Asp or Glu. Another aminoacyl-transferase, termed ATEL1, of the eukaryotic pathogen Plasmodium fakiparum, is a sequelog of prokaryotic L/F-K,F-R-transferases (Aat), but has the specificity of eukaryotic R-D,R-E,R-C*-transferases (ATE1). Phylogenetic analysis suggests that the substrate specificity of R-transferases arose by two distinct routes during the evolution of eukaryotes.
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