Voltage-gated H + channels associated with human phagocyte superoxide-generating NADPH oxidases: Sequence comparisons, structural predictions, and phylogenetic analyses

Abstract

The N-terminal domain of the human phagocyte flavocytochrome b 558 NADPH oxidase, gp91 phox, is believed to be a heme-containing voltage-gated H + channel. The authors have conducted structural, sequence and phylogenetic analyses of the putative transmembrane channel/heme-binding domains of all homologous proteins in the NCBI GenBank database as of May 2001, as well as of the full-length proteins. Fifty-six homologues were identified, including 26 from animals, 19 from plants, seven from yeast, one from a slime mould and three from bacteria. Six well-defined sub-families were revealed by phylogenetic tree construction, two consisting of animal proteins, two of plant proteins, and one each of yeast and bacterial homologues, with the slime mould protein clustering loosely with one of the animal clusters. Signature sequences for the entire family as well as for the sub-families were determined. Most proteins have six putative TMSs, four of which may comprise the heme-binding H + channel. The hydrophobic and amphipathic characteristics of each of the putative &#102 -helical transmembrane segments were defined, and conserved residues that may be involved in heme binding, channel formation, and/or conformational changes were identified. The analyses lead to the suggestion that the oxidase domain became associated with the channel/heme-binding domain to form a single polypeptide chain early in evolutionary history, before eukaryotes diverged from prokaryotes, and that genetic transmission to present day organisms occurred primarily by vertical descent.

• Transmembrane Protein
• Topology
• Channel
• Nadph Oxidase
• Evolution
• Superoxide
• Phylogeny