Substrate specificity of the protease that processes human interleukin-1 beta.
The substrate specificity of the protease which generates mature human interleukin-1 beta (IL-1 beta) from pro-interleukin-1 beta was investigated using synthetic peptide substrates and recombinant pro-IL-1 beta. The requirement of an L-aspartate in the P-1 position was confirmed together with the need for a small hydrophobic residue in the P-1' position (Gly or Ala). It was shown that the enzyme can tolerate conservative substitutions in the P-2 and P-2' positions. We found little difference in the enzyme's ability to cleave denatured and native pro-IL-1 beta, indicating that tertiary structure recognition is not involved in binding. The enzyme did, however, require a peptide of more than six amino acids for cleavage to occur. These results conclusively demonstrate the unusual specificity of this protease.
Department of Protein Chemistry, Immunex Corporation, Seattle, Washington 98101.
P R
PR
Sleath
R C
RC
Hendrickson
S R
SR
Kronheim
C J
CJ
March
R A
RA
Black
D000595:Amino Acid Sequence; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis; D010447:Peptide Hydrolases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity
D007375:Interleukin-1; D009842:Oligopeptides; D010447:Peptide Hydrolases