Human pre-interleukin 1 alpha and beta: structural features revealed by limited proteolysis.
Both pre-interleukin 1 alpha and beta (pre IL 1 alpha and beta) are proteolytically processed into extracellular mature forms of IL 1 alpha and beta. Since pre IL 1 alpha is shown to be biologically active, there may be other reasons for the proteolytic processing of IL 1 alpha and presumably, for IL 1 beta also. In order to examine the possibility that structural stabilization may be associated with the proteolytic processing of pre IL 1 alpha and beta, we investigated the structural features of pre IL 1 alpha and beta by the combination of limited proteolysis and immunoprecipitation with antibodies to the NH2-terminal halves or COOH-terminal halves of pre IL 1 alpha or beta. Both trypsin and V8 protease digested the NH2-terminal halves of pre IL 1 alpha and beta more easily than the COOH-terminal halves of pre IL 1 alpha and beta, yielding structurally stabilized "mature" forms of IL 1. Both trypsin and V8 protease yielded a fragment similar in size to mature IL 1 alpha from pre IL 1 alpha. In contrast, trypsin digested pre IL 1 beta into fragments smaller in size than mature IL 1 beta, while V8 protease yielded a fragment similar in size to mature IL 1 beta. Furthermore, mature IL 1 beta, once processed and released from cells, was resistant to trypsin.(ABSTRACT TRUNCATED AT 250 WORDS)
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick Cancer Research Facility, MD 21701-1013.
Y
Y
Kobayashi
J J
JJ
Oppenheim
K
K
Matsushima
D000818:Animals; D010450:Endopeptidases; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000737:chemistry*; D007536:Isomerism; D008715:Methionine / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry*; D011817:Rabbits; D013462:Sulfur Radioisotopes; D014357:Trypsin
D007375:Interleukin-1; D011498:Protein Precursors; D013462:Sulfur Radioisotopes; C043830:interleukin 1 precursor; D008715:Methionine; D010450:Endopeptidases; D014357:Trypsin