Structural Basis Of Inter-Domain Electron Transfer In Human Ncb5or

FASEB JOURNAL(2010)

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摘要
NADH cytochrome b5 oxidoreductase (Ncb5or) is found in all animals and contains three domains: cytochrome b5 (b5), CHORD-SGT1 (CS) and b5 reductase (b5R). The two redox domains are homologous to microsomal b5 (Cyb5A) and b5R (Cyb5R3), the two known electron donors of stearoyl-CoA desaturase in vitro. To elucidate the structural basis of inter-domain electron transfer in human Ncb5or, we generated individual b5 and b5R domains for structural and kinetic studies. The crystal structure of Ncb5or-b5 was solved by X-ray diffraction with a resolution of 1.95 Å. There are fewer surface charged residues in Ncb5or-b5 than Cyb5A, suggesting a weaker electrostatic interaction in b5-b5R than Cyb5A-Cyb5R3. This was confirmed in our measurements of electron transfer in b5-b5R, Cyb5-Cyb5R3 and mismatched pairs. The linkage through CS likely obviates the need for strong interactions between b5 and b5R in Ncb5or. Ncb5or-b5 has two helix-loop-helix motifs surrounding heme, but differs from Cyb5A in that helix 4 is canted at 45º and shorter. The heme-ligating His112 residue between helix 3 and 4 is displaced due to one-residue deletion (before) and insertion (after). Trp114 in helix 4 of Ncb5or-b5 is a well conserved surface residue potentially involved in inter-domain recognition or electron transfer. We thus conclude that the Ncb5or-b5 core has a conserved b5 scaffold with unique features. (Supported by NIH)
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