Mammalian mitochondrial and microsomal cytochromes b(5) exhibit divergent structural and biophysical characteristics.
The only outer mitochondrial membrane cytochrome b(5) examined to date, from rat (rOM b(5)), exhibits greater stability than known mammalian microsomal (Mc) isoforms, as well as a much higher kinetic barrier for hemin dissociation and a more negative reduction potential. A BlastP search of available databases using the protein sequence of rOM b(5) as template revealed entries for analogous proteins from human (hOM b(5)) and mouse (mOM b(5)). We prepared a synthetic gene coding for the heme-binding domain of hOM b(5), and expressed the protein to high levels. The hOM protein exhibits stability, hemin-binding, and redox properties similar to those of rOM b(5), suggesting that they are characteristic of the OM b(5) subfamily. The divergence in properties between the OM and Mc b(5) isoforms in mammals can be attributed, at least in part, to the presence of two extended hydrophobic patches in the former. The biophysical properties characteristic of the OM proteins may be important in facilitating the two functions proposed for them so far, reduction of ascorbate radical and stimulation of androgen synthesis.
Altuve
Adriana
A
Department of Chemistry, University of Kansas, Lawrence, KS 66047, USA.
Wang
Lijun
L
Benson
David R
DR
Rivera
Mario
M
D000595:Amino Acid Sequence; D000728:Androgens / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015786:Cytochromes b5 / Q000737:chemistry* / Q000502:physiology*; D004247:DNA / Q000737:chemistry; D004563:Electrochemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006418:Heme / Q000737:chemistry; D006427:Hemin / Q000737:chemistry; D006736:Horses; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008861:Microsomes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013696:Temperature; D014466:Ultraviolet Rays
D000728:Androgens; D020033:Protein Isoforms; D006418:Heme; D006427:Hemin; D004247:DNA; D015786:Cytochromes b5