N-End Rule

The N- end rule describes the influence of the N -terminal amino acid of a protein to its rate of degradation.

Properties

The N-terminal amino acid has an influence on the proteolytic degradation of a protein. In the protein, all proteins of eukaryotes or archaea occur with a methionine as the first amino acid or with a formylmethionine in bacteria. Proteins with a different N-terminal amino acid methionine, as can occur in the connection, either by proteolysis or by the removal of methionine by methionine aminopeptidases, provided that the subsequent amino acid valine, glycine, proline, alanine, serine, threonine or cysteine. Of these seven amino acids, however, only leads to an accelerated degradation of cysteine ​​.

There are the two types of N-terminal amino acids and is fed to proteolysis. These two types are called Degrons. The type -1 degron comprises basic amino acids (arginine, lysine and histidine) and the type 2 degron consists of aliphatic amino acids (phenylalanine, tyrosine, tryptophan, leucine, and isoleucine). In bacteria, the detection is carried out by the protein CLPs which supplies a corresponding protein with N -terminal amino acids from degradation by ClpAP. In eukaryotes, these two types are recognized degron by four types of Recogninen, perform a linked protein of the E3 -ubiquitin ligase and therefore a reduction in the ubiquitin -proteasome system.

The degradation preceding arginylation of the N-terminal aspartate, glutamate and Cysteinsulfonsäureresten of a protein is carried out in eukaryotic cells through the arginine -tRNA - protein transferase ATE1. The Cysteinsulfonsäure is an oxidized cysteine ​​and occurs, for example, due to oxidation by nitric oxide or superoxide during the immune response. Aspartic and glutamic acids can be deaminated by two different amidohydrolases to aspartate or glutamate and subsequently provided with arginine. These N -terminal arginylierten proteins are recognized because of the type 1 Degrons (arginine ) of the Recogninen and fed to the ubiquitin ligase.

The oxidation of cysteine ​​to Cysteinsulfonsäure is a sensor for cellular stress. By following the arginylation reduction of the oxidized protein in the proteasome pro-apoptotic proteins and peptides are degraded with oxidized cysteines that initiate cell death in excessive accumulation. In proteins of the human pathogens increased degradation by the N -terminal amino acids could be demonstrated for example in the integrase of HIV and the listeriolysin O of Listeria monocytogenes.

Biological half -lives of N-terminal amino acids

Depending on the species and the amino acid in N-terminal position of these have different half-lives:

  • Arg, Lys, Phe, Leu, Trp, Tyr
  • All others:
  • 2 min
  • > 10 h
  • Met, Gly, Ala, Ser, Thr, Val, Cys
  • Per
  • Ile, Glu
  • Tyr, Gln
  • Leu, Phe, Trp, Asp, Asn, Lys, His
  • Bad
  • > 30 h
  • 5 h
  • 30 min
  • 10 min
  • 3 min
  • 2 min
  • Val
  • Met, Gly
  • Pro, Ile
  • Thr
  • Leu
  • Ala
  • His
  • Trp, Tyr
  • Ser
  • Asn
  • Lys
  • Cys
  • Asp, Phe
  • Glu, Arg
  • Gln
Deamination Biological half-life Digital Object Identifier
225855
de