Intramembrane bis-heme motif for transmembrane electron transport conserved in a yeast iron reductase and the human NADPH oxidase.
A plasma membrane iron reductase, required for cellular iron acquisition by Saccharomyces cerevisiae, and the human phagocytic NADPH oxidase, implicated in cellular defense, contain low potential plasma membrane b cytochromes that share elements of structure and function. Four critical histidine residues in the FRE1 protein of the iron reductase were identified by site-directed mutagenesis. Individual mutation of each histidine to alanine eliminated the entire heme spectrum without affecting expression of the apoprotein, documenting the specificity of the requirement for the histidine residues. These critical residues are predicted to coordinate a bis-heme structure between transmembrane domains of the FRE1 protein. The histidine residues are conserved in the related gp91(phox) protein of the NADPH oxidase of human granulocytes, predicting the sites of heme coordination in that protein complex. Similarly spaced histidine residues have also been implicated in heme binding by organelle b cytochromes with little overall sequence similarity to the plasma membrane b cytochromes. This bis-heme motif may play a role in transmembrane electron transport by distinct families of polytopic b cytochromes.
Finegold
A A
AA
Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Shatwell
K P
KP
Segal
A W
AW
Klausner
R D
RD
Dancis
A
A
D000483:Alleles; D000595:Amino Acid Sequence; D003573:Cytochrome b Group / Q000378:metabolism; D004579:Electron Transport; D038181:FMN Reductase; D006418:Heme / Q000378:metabolism*; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment
D003573:Cytochrome b Group; D006418:Heme; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C023903:ferric citrate iron reductase