How BamA recruits OMP substrates via poly-POTRAs domain
How BamA recruits OMP substrates via poly-POTRAs domain
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BamA 如何通过聚 POTRA 结构域招募 OMP 底物
DOI：
10.1096/fj.201900681rr
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Meng Guoyu
中科院分区：
文献类型：
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作者：
Ma Xiaodan;Wang Qianqian;Li Yuwen;Tan Pan;Wu Haiyan;Wang Pengran;Dong Xue;Hong Liang;Meng Guoyu
几乎所有的外膜蛋白都通过多肽转运相关基序和β-Barrel组装机制折叠成一个不变的β-Barrel折叠。然而，Poly-POTRA是否以及如何与OMP相互作用在很大程度上仍不清楚。在这里，我们对流感嗜血杆菌的结构进行了表征，包括X射线结晶学、小角X射线散射和分子动力学模拟。出人意料的是，晶体堆积揭示了一条推测的omp旅行路径，该路径由Poly-POTRA中保守的α2-β2边螺旋排列。另一方面，针对OMP结合位点的基于结构的突变显著扰乱了OMP的生物发生，导致严重的细胞生长缺陷。另一个值得注意的特点是。影响POTRA结构的是灵活性。酶联免疫吸附试验表明，Poly-POTRAs能够以分步方式募集OMP底物。更重要的是，Potra-Potra的连锁和灵活性的限制显著削弱了BAMA功能，导致细胞生长缺陷。综上所述，这些结果表明β链的扩增和内在的灵活性是BAMA-OMP招募的重要因素。-Ma，X.，Wang，Q.，Li，Y.，Tan，P.，Wu，H.，Wang，P.，董，X.，Hong，L.，Meng，G.BAMA如何通过apoly-POTRAS结构域招募OMP底物。FASE B J.33,14690-14702(2019年)。Www.fasebj.org
Almost all the outer membrane proteins (OMPs) fold into an invariant β‐barrel foldviathe polypeptide‐transport‐associated (POTRA) motif and β‐barrel assembly machinery (BAM). However, whether and how poly‐POTRAs interact with OMPs remain largely unknown. Here, we have characterized the structures ofHaemophilus influenzaepoly‐POTRAsviaX‐ray crystallography, small angle X‐ray scattering, and molecular dynamics simulation. Unexpectedly, crystal packing reveals a putative OMP travel pathway spiraled by the conserved α2‐β2 edges in poly‐POTRAs. Supportively, the structure‐based mutations targeting the OMP binding sites significantly disrupt OMP biogenesis, resulting in severe cell growth defects. Another notable feature inH. influenzaePOTRA structures is flexibility. As characterized by ELISA assays, poly‐POTRAs could recruit OMP substrates in a step‐wise manner. More importantly, the restriction of POTRA‐POTRA linkage and flexibility significantly impairs the BamA function and causes cell growth defect. Altogether, these results suggest that the β‐strand augmentations and intrinsic flexibility are important factors for BamA‐OMP recruitment.—Ma, X., Wang, Q., Li, Y., Tan, P., Wu, H., Wang, P., Dong, X., Hong, L., Meng, G. How BamA recruits OMP substratesviapoly‐POTRAs domain. FASEB J. 33, 14690‐14702 (2019). www.fasebj.org