Posttranslational deamidation of proteins: The case of hemoglobin J Sardegna [alpha 50(CD8)His -> Asn -> Asp]

Hemoglobin J Sardegna [alpha 50(CD8)His-->Asn-->Asp] is a human Hb variant in which a posttranslational deamidation process takes place, transforming an Asn to an Asp residue. This variant, particularly widespread in northern Sardinia, has for the first time been characterized at the DNA level (codo n 50 C-->A) on the selectively amplified alpha(2)-globin gene. We determine d the protein and DNA sequences and performed cellulose acetate electrophor esis, isoelectric focusing, globin chain separation, stability tests with i sopropanol and heat precipitation, and oxygen affinity analyses on whole bl ood to fully characterize the variant. A comprehensive review of the deamid ation processes involving Asn and Gin residues in mutant proteins is report ed, together with a discussion of the molecular mechanisms of such deamidat ions. Finally, examples of other proteins of clinical importance in which A sn or Gin residues have been implicated by DNA analysis alone are presented . These findings point out the importance of the complete characterization of variant proteins by use of both DNA and protein analyses.