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DCS‐1, DCS‐2, and DFV share amino acid substitutions at the extracellular RhD protein vestibule
Author(s) -
Flegel Willy A.,
Von Zabern Inge,
Doescher Andrea,
Wagner Franz F.,
Vytisková Jindra,
Písačka Martin
Publication year - 2008
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2007.01506.x
Subject(s) - extracellular , vestibule , chemistry , amino acid , microbiology and biotechnology , biology , biochemistry , neuroscience , vestibular system
BACKGROUND: RhD and RhCE are structurally related to ammonium transporter proteins, yet their physiologic function remains unclear. Recent three‐dimensional homology modeling with Escherichia coli AmtB as a template defined a putative transmembraneous channel. Three RhD variants with amino acid substitutions located at the extracellular channel aperture are described. STUDY DESIGN AND METHODS: Blood samples were selected because of serologic abnormalities. RHD, RHCE, and LW nucleotide sequences were determined from genomic DNA. D epitope patterns were established with monoclonal anti‐D panels. Three‐dimensional Rh structures were calculated by alignment to AmtB. RESULTS: The RHD allele DCS‐1 was found to carry the two amino acid substitutions F223V (667T > G) and A226P (676G > C) caused by missense mutations in RHD exon 5. This study compared DCS‐1 with the D variants DFV (F223V) and DCS‐2 (A226P) , harboring solely one or the other of the two substitutions. All three D variants were associated with a cDE haplotype. The antigen densities were approximately 3000 D antigens per red blood cell for DCS‐1, 800 for DCS‐2, and 9300 for DFV. DCS‐1 and DCS‐2 were partial D, because they lacked distinct epitopes. DFV presented as an almost normal D phenotype; the sample contained allo‐anti‐LW a . The D w antigen was absent from DCS‐1, DFV, and DAU‐4, but expressed by DAU‐5. CONCLUSION: DCS‐1, DCS‐2, and DFV carry amino acid substitutions at the extracellular vestibule, visualized by 3‐dimensional modeling. Proline at position 226 greatly influenced the D antigen density and may reduce the RhD membrane integration. Although the F223V substitution is regarded as the initial event in the evolution of the weak D Type 4 cluster, the current DFV allele probably evolved independently, as evident from different RHCE haplotypes.