A 3-dimensional trimeric β-barrel model for Chlamydia MOMP contains conserved and novel elements of Gram-negative bacterial porins.

A 3-dimensional trimeric β-barrel model for Chlamydia MOMP contains conserved and novel elements of Gram-negative bacterial porins.
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DOI:
10.1371/journal.pone.0068934
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Amaro RE
Amaro RE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Feher VA;Randall A;Baldi P;Bush RM;de la Maza LM;Amaro RE

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沙眼衣原体是细菌性性传播疾病的最常见原因,也是全世界可预防性失明的主要原因。对衣原体的全面控制最好通过疫苗来实现,其主要目标是主要外膜蛋白 MOMP,它占该细菌外膜蛋白质量的约 60%。由于缺乏 MOMP 的实验结构信息,之前发布的三个拓扑模型假定采用 16 股桶状结构。在这里,我们使用最新的 β 桶预测算法、先前的 2D 拓扑建模结果和比较建模方法来构建基于 16 链三聚体假设的 3D 模型。我们发现,虽然 3D MOMP 模型捕获了三聚体 16 链 β-桶孔蛋白的许多结构特征,并且与 MOMP 的大多数实验证据一致,但 MOMP 残基 320-334 不能建模为跨越整个膜的 β-链,正如在已发表的 16 链 β-桶晶体结构中一致观察到的那样。鉴于本研究中发现的 β 链描绘结果不明确,最近发表的膜 β 桶结构打破了偶数 β 链的规范规则,β 桶具有链交换寡聚构象的发现,以及取决于细菌生命周期的交替折叠,我们建议,尽管 MOMP 孔蛋白结构包含规范的 16 链构象,但它可能具有新颖的寡聚或动态结构变化解释观察到的差异。
Chlamydia trachomatis is the most prevalent cause of bacterial sexually transmitted diseases and the leading cause of preventable blindness worldwide. Global control of Chlamydia will best be achieved with a vaccine, a primary target for which is the major outer membrane protein, MOMP, which comprises ∼60% of the outer membrane protein mass of this bacterium. In the absence of experimental structural information on MOMP, three previously published topology models presumed a16-stranded barrel architecture. Here, we use the latest β-barrel prediction algorithms, previous 2D topology modeling results, and comparative modeling methodology to build a 3D model based on the 16-stranded, trimeric assumption. We find that while a 3D MOMP model captures many structural hallmarks of a trimeric 16-stranded β-barrel porin, and is consistent with most of the experimental evidence for MOMP, MOMP residues 320–334 cannot be modeled as β-strands that span the entire membrane, as is consistently observed in published 16-stranded β-barrel crystal structures. Given the ambiguous results for β-strand delineation found in this study, recent publications of membrane β-barrel structures breaking with the canonical rule for an even number of β-strands, findings of β-barrels with strand-exchanged oligomeric conformations, and alternate folds dependent upon the lifecycle of the bacterium, we suggest that although the MOMP porin structure incorporates canonical 16-stranded conformations, it may have novel oligomeric or dynamic structural changes accounting for the discrepancies observed.
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