Dynamic interplay between the periplasmic chaperone SurA and the BAM complex in outer membrane protein folding.

Dynamic interplay between the periplasmic chaperone SurA and the BAM complex in outer membrane protein folding.
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DOI:
10.1038/s42003-022-03502-w
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发表时间:
2022-06-08
影响因子:
5.9
通讯作者:
--
中科院分区:
生物学2区
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--
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外膜蛋白(OMP)正确折叠到革兰氏阴性菌的外膜中取决于将未折叠的OMP递送到β-桶组装机器(BAM)。如何展开基板BAM仍然难以捉摸,但主要的OMP分子伴侣SurA提出发挥关键作用。在这里,我们已经使用氢氘交换质谱(HDX-MS),交联,体外折叠和结合试验和计算建模,以显示SurA的核心结构域和它的两个PPIase结构域之一是关键的SurA-BAM相互作用,并需要最大催化OMP折叠。我们发现,结合导致BAM和SurA构象和/或动力学的变化,包括在BamA β1-β16接缝的结合位点的远端。我们提出了一个模型OMP的生物合成中,SurA起着至关重要的作用,OMP交付和总理BAM接受折叠基板。外膜蛋白(OMP)伴侣SurA和OMP折叠催化剂BAM的相互作用导致两个物种的构象集合的变化,这表明在革兰氏阴性菌中将OMP递送至BAM的机制。
Correct folding of outer membrane proteins (OMPs) into the outer membrane of Gram-negative bacteria depends on delivery of unfolded OMPs to the β-barrel assembly machinery (BAM). How unfolded substrates are presented to BAM remains elusive, but the major OMP chaperone SurA is proposed to play a key role. Here, we have used hydrogen deuterium exchange mass spectrometry (HDX-MS), crosslinking, in vitro folding and binding assays and computational modelling to show that the core domain of SurA and one of its two PPIase domains are key to the SurA-BAM interaction and are required for maximal catalysis of OMP folding. We reveal that binding causes changes in BAM and SurA conformation and/or dynamics distal to the sites of binding, including at the BamA β1-β16 seam. We propose a model for OMP biogenesis in which SurA plays a crucial role in OMP delivery and primes BAM to accept substrates for folding. Interaction of the outer membrane protein (OMP) chaperone SurA and the OMP folding catalyst BAM results in changes in the conformational ensembles of both species, suggesting a mechanism for delivery of OMPs to BAM in Gram-negative bacteria.
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