Detection of gp91-phox precursor protein in B-cell lines from patients with X-linked chronic granulomatous disease as an indicator for mutations impairing cytochrome b558 biosynthesis.
NADPH oxidase cytochrome b558 consists of two subunits, gp91-phox and p22-phox, defects of which result in chronic granulomatous disease (CGD). The nature of the interaction between these subunits has yet to be determined. Absence of p22-phox in autosomal CGD patient-derived B-cell lines results in detectable levels of an incompletely glycosylated gp91-phox precursor. We have detected this same precursor species in four cell lines from patients with the X-linked form of the disease due to mutations in gp91-phox. Such mutations should delineate regions of gp91-phox important for its biosynthesis, including stable association with p22-phox. One mutation mapped to the putative FAD-binding domain, one mapped to a potential haem-binding domain, and two involved the region encoded by exon 3.
Porter
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Division of Cell and Molecular Biology, Institute of Child Health, London, U.K.
Kuribayashi
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F
Parkar
M H
MH
Roos
D
D
Kinnon
C
C
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003573:Cytochrome b Group / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D008040:Genetic Linkage; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D009252:NADPH Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014960:X Chromosome
D003573:Cytochrome b Group; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D011498:Protein Precursors; D006418:Heme; C036888:cytochrome b558; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase