Folding of a bacterial integral outer membrane protein is initiated in the periplasm.
Folding of a bacterial integral outer membrane protein is initiated in the periplasm.
复制标题
细菌完整外膜蛋白的折叠在周质中启动。
DOI：
10.1038/s41467-017-01246-4
复制
发表时间：
2017
影响因子：
16.6
通讯作者：
Bernstein,HarrisD
中科院分区：
文献类型：
--
作者：
Sikdar,Rakesh;Peterson,JanineH;Anderson,DEric;Bernstein,HarrisD
Bam复合物促进β-桶蛋白插入细菌外膜，但尚不清楚它是否以逐步方式将β-链穿入脂质双层或催化预折叠底物的插入。在这里，为了区分这两种可能性，我们分析了UpaG，一个三聚体的自转运粘附素（TAA）的生物起源。TAA由三个相同的亚基组成，它们一起形成单个β-桶结构域和细胞外卷曲螺旋（“过客”）结构域。使用位点特异性光交联来获得对UpaG组装的空间和时间见解，我们表明UpaG β-桶片段在周质中折叠成三聚体结构，该结构持续到乘客结构域易位终止。除了获得至少一些β桶蛋白在与Bam复合物相互作用之前开始折叠的证据外，我们还确定了一类特征不明确的毒力因子组装中的几个离散步骤。
The Bam complex promotes the insertion of β-barrel proteins into the bacterial outer membrane, but it is unclear whether it threads β-strands into the lipid bilayer in a stepwise fashion or catalyzes the insertion of pre-folded substrates. Here, to distinguish between these two possibilities, we analyze the biogenesis of UpaG, a trimeric autotransporter adhesin (TAA). TAAs consist of three identical subunits that together form a single β-barrel domain and an extracellular coiled-coil (“passenger”) domain. Using site-specific photocrosslinking to obtain spatial and temporal insights into UpaG assembly, we show that UpaG β-barrel segments fold into a trimeric structure in the periplasm that persists until the termination of passenger-domain translocation. In addition to obtaining evidence that at least some β-barrel proteins begin to fold before they interact with the Bam complex, we identify several discrete steps in the assembly of a poorly characterized class of virulence factors.