NADPH oxidase subunit gp91phox: a proton pathway.
The generation of superoxide by the NADPH oxidase is an electrogenic process resulting in a rapid depolarisation of the membrane potential of the cell. The efflux of H+ ions through an arachidonate-activatable, Zn(2+)-inhibitable H+ pathway accompanies the efflux of electrons and provides the necessary charge compensation. Inhibition of H+ flux leads to inhibition of superoxide generation. The protein gp91phox, a transmembrane component of the NADPH oxidase, was demonstrated to be capable of acting as the NADPH oxidase-associated H+ channel in a stable CHO cell line, CHO91. The N-terminal 230 amino acids contain all that is required for the protein to form an H+ channel and specifically histidine 115 is important to the ability of gp91phox to conduct H+ ions. The recording of outward currents from CHO91 cells, in the whole-cell configuration, demonstrated that gp91phox is also capable of functioning as a voltage-gated H+ conductance pathway. The similarity in properties between voltage-elicited outward currents, from both wild type and the mutations, and the arachidonate-activated H+ flux strongly suggests that these H+ pathways are one in the same. Among the recently identified homologues of gp91phox only NOH-1S has so far been demonstrated to also act as an H+ conductance pathway.
Henderson
L M
LM
Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD, United Kingdom.
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011522:Protons
D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011522:Protons; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases