The effect of amino acid substitutions at position 342 on the secretion of human alpha 1-antitrypsin from Xenopus oocytes.
A glutamic acid to lysine change in the Z variant of human alpha 1-antitrypsin is associated with a failure to secrete the protein from synthesising cells. The block in export of the protein may be caused either by the loss of an acidic residue or the introduction of a basic one at this point in the polypeptide chain. Site-directed mutagenesis has been used to construct novel alpha 1-antitrypsin mutants which show that the side chain interactions from Glu-342 are not obligatory for protein export and it is rather the introduction of a basic residue at this point which produces the intracellular accumulation of the protein.
Wu
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Department of Physiology and Pharmacology, University of Southampton, UK.
Foreman
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RC
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009865:Oocytes; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D012492:Salts; D013329:Structure-Activity Relationship; D014982:Xenopus laevis; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism*
D011994:Recombinant Proteins; D012492:Salts; D000515:alpha 1-Antitrypsin