タンパク質の精密質量決定の生物学的意義

Abstract

Achievement of the unit mass accuracy in the molecular mass determination of proteins has been stressed. Single mass change of proteins is caused by single amino acid substitutions including Glu/Lys, Asn/Leu, Asn/Ile, Asp/Asn, and Glu/Gln, of which four mutations except for Asn/Leu are produced by single nucleotide changes. In the case of Hemoglobin Hoshida, a substitution of Asn for Asp was found in a peptide of 2056.9 Da with a decrease of single mass unit. In a structural study of the transferrin isoform which is characteristic of carbohydrate-deficient glycoprotein syndrome and missing asparagine-linked oligosaccharides, assignment of Asn but not Asp for the residue that should be glycosylated was necessary for delineating the molecular pathogenesis of this disorder. However, as demonstrated in β2-microglobulin, proteins are often partially deamidated during sample preparation or in vivo. This may compromise the biological significance of the precise mass measurement of proteins.