Disruption of the Lys-290--Glu-342 salt bridge in human alpha 1-antitrypsin does not prevent its synthesis and secretion.
The object of this work was to test the hypothesis that failure to secrete the Z variant of human alpha 1-antitrypsin is related to the loss of a particular structural feature, the Lys-290 to Glu-342 salt bridge. Oligonucleotide-directed mutagenesis was used to disrupt the salt bridge by substituting a glutamic acid for lysine at residue 290. RNA transcripts prepared from this mutant DNA and from the normal cDNA were both able to direct the synthesis of protein in a cell-free system and after injection into Xenopus oocytes. Furthermore, the constructed mutant alpha 1-antitrypsin was secreted as readily as the normal inhibitor.
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000235:genetics; D005260:Female; D005971:Glutamates; D018698:Glutamic Acid; D006801:Humans; D008239:Lysine; D009154:Mutation; D009865:Oocytes; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D014981:Xenopus; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D005971:Glutamates; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin; D018698:Glutamic Acid; D004247:DNA; D008239:Lysine