The primary structure of human ribonuclease/angiogenin inhibitor (RAI) discloses a novel highly diversified protein superfamily with a common repetitive module.
Immunological screening of a lambda gt11 library, constructed from HeLa mRNA, yielded several ribonuclease/angiogenin inhibitor (RAI) cDNA clones containing 900-bp inserts. Northern blot analysis revealed that the length of the RAI mRNA is approximately 1.9 kb. Construction and screening of a eukaryotic cDNA expression library (HeLa) containing preferentially complete cDNA inserts led to the isolation of a full length clone. The complete nucleotide sequence was determined. The C-terminal amino acid sequence deduced from the cDNA is identical to the peptide sequence obtained from a CNBr fragment of RAI, confirming the identity of the clone. The deduced primary structure of RAI consists of eight homologous tandem repeats with remarkable periodicity of leucine and cysteine residues. Each repeat is derived from the duplication of a leucine-rich 28-amino-acid module. This prototype module is closely related to a repetitive 24-amino-acid motif of unclear function, previously found in proteins involved in important biological processes such as blood coagulation, embryonic development, cell morphogenesis and signal transduction. Although homologous, the RAI modules show distinct differences in length and amino acid composition to the modules of this group of proteins, demonstrating their high potential of variability, necessary for adaptation to very diverse roles. Based on our results we propose that these repetitive modules are a common structural feature of a novel protein superfamily whose members exert their function by highly specific protein-protein interactions.
Schneider
R
R
Institute of Biochemistry, University of Innsbruck, Austria.
Schneider-Scherzer
E
E
Thurnher
M
M
Auer
B
B
Schweiger
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010926:Placental Hormones / Q000235:genetics*; D011506:Proteins / Q000037:antagonists & inhibitors; D012259:Ribonuclease, Pancreatic; D012260:Ribonucleases / Q000037:antagonists & inhibitors*
D010926:Placental Hormones; D011506:Proteins; C022052:placental ribonuclease inhibitor; D004247:DNA; D012260:Ribonucleases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic