Hop-family Helicobacter outer membrane adhesins form a novel class of Type5-like secretion proteins with an interrupted β-barrel domain
Hop-family Helicobacter outer membrane adhesins form a novel class of Type5-like secretion proteins with an interrupted β-barrel domain
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DOI：
10.1111/mmi.14075
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发表时间：
2018-10-01
影响因子：
3.6
通讯作者：
Remaut, Han
中科院分区：
文献类型：
--
作者：
Coppens, Fanny;Castaldo, Gaetano;Remaut, Han
人类胃病原体幽门螺杆菌通过螺杆菌外膜蛋白（Hops）的旁系同源家族的成员附着于健康和发炎的胃组织，所述旁系同源家族的成员包括粘附素BabA、SabA、HopQ、LabA和HopZ。啤酒花共享一个保守的25 kDa的C-末端区域，被认为是形成一个自身转运蛋白样跨膜结构域。相反，我们的研究结果表明，啤酒花含有一个非连续的跨膜结构域，由七个预测的-链在C-末端和一个在N-末端。C-末端结构域的折叠和外膜定位关键取决于前16个N-末端残基内的预测跨膜链。显示N-末端驻留在周质中，并且我们的SabA细胞外结构域的晶体和小角度X射线散射结构揭示了连接至跨膜链1和2的保守卷曲螺旋茎结构域。综上所述，我们的数据表明，啤酒花粘附素代表了一种新的外膜蛋白拓扑结构，包括OmpA样8链桶，其被插入第一胞外环内的15-108 kDa结构域中断。在细胞外环中插入大的折叠结构域在细菌外膜蛋白中是前所未有的，并且预计对这些蛋白质如何到达细胞表面具有重要影响。
The human stomach pathogen Helicobacter pyloriattaches to healthy and inflamed gastric tissue through members of a paralogous family of Helicobacter outer membrane proteins' (Hops), including adhesins BabA, SabA, HopQ, LabA and HopZ. Hops share a conserved 25 kDa C-terminal region that is thought to form an autotransporter-like transmembrane domain. Instead, our results show that Hops contain a non-continuous transmembrane domain, composed of seven predicted -strands at the C-terminus and one at the N-terminus. Folding and outer membrane localization of the C-terminal -domain critically depends on a predicted transmembrane -strand within the first 16 N-terminal residues. The N-terminus is shown to reside in the periplasm, and our crystal and small angle X-ray scattering structures for the SabA extracellular domain reveal a conserved coiled-coil stem domain that connects to transmembrane -strand 1 and 2. Taken together, our data show that Hop adhesins represent a novel outer membrane protein topology encompassing an OmpA-like 8-stranded -barrel that is interrupted by a 15-108 kDa domain inserted inside the first extracellular loop. The insertion of large, folded domains in an extracellular loop is unprecedented in bacterial outer membrane proteins and is expected to have important consequences on how these proteins reach the cell surface.