Missense mutations outside the catalytic domain of the ABO glycosyltransferase can cause weak blood group A and B phenotypes
Copyright policy )Missense mutations outside the catalytic domain of the ABO glycosyltransferase can cause weak blood group A and B phenotypes
BACKGROUND: Only little is known about the impact of amino acid substitutions outside an enzyme's active site on A and B transferase activity.STUDY DESIGN AND METHODS: A panel of blood group A‐ and B‐specific plasmids containing the six known missense mutations of the coding sequence upstream of exon 6 of the ABO gene were constructed. HeLa cells were used to transfect ABO expression plasmids.RESULTS: Expression of ABO variants containing single or multiple missense mutations in HeLa cells resulted in a significant decrease in the percentage of antigen‐expressing cells (up to 29%) and in mean fluorescence intensity (MFI; up to 50%) compared to transfection with ABO*A101 or ABO*B101. Coexpression of the respective antithetical wild‐type construct (ABO*A101 and ABO*B101, respectively) further reduced cell surface expression of variant ABO constructs in regard to the percentage of expressing cells (up to 53% decrease) and MFI (up to 59% decrease).CONCLUSION: Weak A and B subgroups can arise from transferases with amino acid changes in the N‐terminal domain, particularly in AB phenotypes, where normal A1 or B1 glycosyltransferases compete for the same substrates.
- Hannover Medical School Germany
Models, Molecular, Protein Conformation, Recombinant Fusion Proteins, Mutation, Missense, Exons, Galactosyltransferases, Transfection, ABO Blood-Group System, Protein Structure, Tertiary, Phenotype, Amino Acid Substitution, Humans, N-Acetylgalactosaminyltransferases, Codon, Alleles, HeLa Cells
Models, Molecular, Protein Conformation, Recombinant Fusion Proteins, Mutation, Missense, Exons, Galactosyltransferases, Transfection, ABO Blood-Group System, Protein Structure, Tertiary, Phenotype, Amino Acid Substitution, Humans, N-Acetylgalactosaminyltransferases, Codon, Alleles, HeLa Cells
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