Modelling the human rhesus proteins: implications for structure and function.
The mammalian rhesus (Rh) proteins that carry the Rh blood group antigens of red blood cells are related to the ammonium channel (Amt) proteins found in both pro- and eukaryotes. However, despite their clinical importance the structure of the Rh antigens is presently unknown. We have constructed homology models of the human Rh proteins, RhD and RhAG using the structure of the Escherichia coli ammonia channel AmtB as a template, together with secondary structure predictions and the extensive available biochemical data for the Rh proteins. These models suggest that RhAG and the homologous non-erythrocyte Rhesus glycoproteins, RhBG and RhCG, have a very similar channel architecture to AmtB. By comparison, RhD and RhCE have a different arrangement of residues, indicating that if they function as ammonia channels at all, they must do so by a different mechanism. The E. coli AmtB protein is a homotrimer and our models provoke a reassessment of the widely accepted tetrameric model of the organisation of the erythrocyte Rh complex. A critical analysis of previously published data, together with sequencing yield data, lead us to suggest that the erythrocyte Rh complex could indeed also be trimeric.
Conroy
Matthew J
MJ
Department of Molecular Biology and Biotechnology, Krebs Institute for Biomolecular Research, University of Sheffield, Sheffield, UK.
Bullough
Per A
PA
Merrick
Mike
M
Avent
Neil D
ND
D000595:Amino Acid Sequence; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D012204:Rh-Hr Blood-Group System / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
C111096:AmtB protein, E coli; D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; D000644:Quaternary Ammonium Compounds; D012204:Rh-Hr Blood-Group System