Molecular basis of the D variant phenotypes DNU and D II allows localization of critical amino acids required for expression of Rh D epitopes epD3, 4 and 9 to the sixth external domain of the Rh D protein
Autor: | Wendy Liu, Franz F. Wagner, Charles Green, M. Scott, Jeffrey W. Jones, Neil D. Avent, Willy A. Flegel, D. Voak |
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Rok vydání: | 1997 |
Předmět: |
chemistry.chemical_classification
Erythrocytes Rh-Hr Blood-Group System Sequence analysis Point mutation Hematology Biology Molecular biology Epitope Amino acid Epitopes Exon Phenotype Epitope mapping Protein structure chemistry Biochemistry Humans Point Mutation Amino Acids Cloning Molecular Rh blood group system Epitope Mapping |
Zdroj: | British Journal of Haematology. 97:366-371 |
ISSN: | 1365-2141 0007-1048 |
DOI: | 10.1046/j.1365-2141.1997.632710.x |
Popis: | The discovery of Rh partial D variant red cells by discrepant reactions with different monoclonal anti-D has demonstrated the range of Rh D epitopes that have arisen due to alterations in Rh D protein structure. There are two current classification systems. one which uses a nine epitope model (epDl-epD9l whereas a more recent model proposes 3() different epitopes. we describe here the molecular basis of two D variants which lack epD4 and epD9 namely the DNU and D II phenotypes. These would have both been originally classified as D II phenotype individuals, but we have revealed subtle differences in the serological profile of these erythrocytes. Such a differential reactivity and determination of the molecular bases of these phenotypes allows us to predict critical amino acids for epD3. epD4 and epD9 expression. The DNU phenotype arises from a single point mutation in the RHD gene resulting in a single amino acid change (Gly353 Arg). Sequence analysis of exon 7 of the RHD gene derived from the D II propositus indicates that there is a single point mutation in this exon resulting in a single amino acid change (Ala 354Asp). It is likely that this point mutation gives rise to the D II phenotype. Both mutations result in the change to Rh D-specific residues. Our results indicate that the following amino acids are crucial for epD 3a (Asp 350 ). epD3b (Asp 350 + Gly 393 ), epD4a (Gly 353 + Ala 354 ), epD4b (Ala 354 , epD9a (Asp 350) +Gly 353 +Ala 354 ) and epD9b (Asp 350 + Ala 354 ) expression. All of these amino acids reside on the predicted sixth external domain of the RhD protein, so it is possible that epD3, 4 and 9 are continuous epitopes. |
Databáze: | OpenAIRE |
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