Crystal structure of the DsbB-DsbA complex reveals a mechanism of disulfide bond generation

被引:204
作者
Inaba, Kenji
Murakami, Satoshi
Suzuki, Mamoru
Nakagawa, Atsushi
Yamashita, Eiki
Okada, Kengo
Ito, Koreaki
机构
[1] Japan Sci & Technol Agcy, CREST, Kyoto 6068507, Japan
[2] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
[3] Osaka Univ, Inst Sci & Ind Res, Osaka 5670047, Japan
[4] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan
[5] Nara Inst Sci & Technol, Nara 6300192, Japan
[6] Kyoto Univ, Inst Virus Res, Kyoto 6068507, Japan
基金
日本科学技术振兴机构;
关键词
D O I
10.1016/j.cell.2006.10.034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidation of cysteine pairs to disulfide requires cellular factors present in the bacterial periplasmic space. DsbB is an E coli membrane protein that oxidizes DsbA, a periplasmic dithiol oxidase. To gain insight into disulfide bond formation, we determined the crystal structure of the DsbB-DsbA complex at 3.7 angstrom resolution. The structure of DsbB revealed four transmembrane helices and one short horizontal helix juxtaposed with Cys130 in the mobile periplasmic loop. Whereas DsbB in the resting state contains a Cys104-Cys130 disulfide, Cys104 in the binary complex is engaged in the intermolecular disulfide bond and captured by the hydrophobic groove of DsbA, resulting in separation from Cys130. This cysteine relocation prevents the backward resolution of the complex and allows Cys130 to approach and activate the disulfide-generating reaction center composed of Cys41, Cys44, Arg48, and ubiquinone. We propose that DsbB is converted by its specific substrate, DsbA, to a superoxidizing enzyme, capable of oxidizing this extremely oxidizing oxidase.
引用
收藏
页码:789 / 801
页数:13
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