Transmembrane helices mediate the formation of a stable ternary complex of b(5)R, cyt b(5), and SCD1.

Transmembrane helices mediate the formation of a stable ternary complex of b(5)R, cyt b(5), and SCD1.
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DOI:
10.1038/s42003-022-03882-z
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发表时间:
2022-09-12
影响因子:
5.9
通讯作者:
--
中科院分区:
生物学2区
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哺乳动物细胞色素b5 (cyt b5)和细胞色素b5还原酶(b5R)是膜包埋氧化还原酶的电子载体蛋白。b5R和cyt b5都具有胞质结构域和单个跨膜螺旋结构。b5R和cyt b5的胞质结构域含有电子转移所需的辅助因子,但目前尚不清楚TM螺旋是否具有除了作为膜锚点之外的功能。在这里,我们发现b5R和cyt b5形成一个稳定的二元配合物,cyt b5和硬脂酰辅酶a去饱和酶-1 (SCD1)也是如此。我们还发现b5R、cyt b5和SCD1形成稳定的三元配合物。我们证明了TM螺旋是组装稳定的二元和三元配合物所必需的,在这些配合物中电子转移速率大大提高。这些结果揭示了TM螺旋在cyt b5和b5R中的作用,并表明由稳定的三元配合物组成的电子传递链可能是需要cyt b5和b5R的膜嵌入氧化还原酶的普遍特征。哺乳动物细胞色素b5 (cyt b5), cyt b5还原酶(b5R)和硬脂酰辅酶a去饱和酶-1 (SCD1)的跨膜结构域在cyt b5/b5R或cyt b5/SCD1之间形成稳定的二元配合物和三元配合物,从而提高电子传递速率。
Mammalian cytochrome b5 (cyt b5) and cytochrome b5 reductase (b5R) are electron carrier proteins for membrane-embedded oxidoreductases. Both b5R and cyt b5 have a cytosolic domain and a single transmembrane (TM) helix. The cytosolic domains of b5R and cyt b5 contain cofactors required for electron transfer, but it is not clear if the TM helix has function beyond being an anchor to the membrane. Here we show that b5R and cyt b5 form a stable binary complex, and so do cyt b5 and stearoyl-CoA desaturase-1 (SCD1). We also show that b5R, cyt b5 and SCD1 form a stable ternary complex. We demonstrate that the TM helices are required for the assembly of stable binary and ternary complexes where electron transfer rates are greatly enhanced. These results reveal a role of the TM helix in cyt b5 and b5R, and suggest that an electron transport chain composed of a stable ternary complex may be a general feature in membrane-embedded oxidoreductases that require cyt b5 and b5R. The transmembrane domains of mammalian cytochrome b5 (cyt b5), cyt b5 reductase (b5R), and stearoyl-CoA desaturase-1 (SCD1) form stable binary complexes between cyt b5/b5R or cyt b5/SCD1 and a ternary complex, which enhance electron transfer rates.
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