Display Settings:

Format

Send to:

Choose Destination
Transfusion. 2008 Jan;48(1):25-33. Epub 2007 Sep 27.

DCS-1, DCS-2, and DFV share amino acid substitutions at the extracellular RhD protein vestibule.

Author information

  • 1Institute for Transfusion Medicine, University Hospital Ulm, Ulm Germany. willy.flegel@uni-ulm.de

Abstract

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 3,000 D antigens per red blood cell for DCS-1, 800 for DCS-2, and 9,300 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.

PMID:
17900276
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Blackwell Publishing
    Loading ...
    Write to the Help Desk