Structural characterization of the POTRA domains from A. baumannii reveals new conformations in BamA

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2024-09-17 DOI:10.1016/j.str.2024.08.013

Claire Overly Cottom, Robert Stephenson, Dante Ricci, Lixinhao Yang, James C. Gumbart, Nicholas Noinaj

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Abstract

Recent studies have demonstrated BamA, the central component of the β-barrel assembly machinery (BAM), as an important therapeutic target to combat infections caused by Acinetobacter baumannii and other Gram-negative pathogens. Homology modeling indicates BamA in A. baumannii consists of five polypeptide transport-associated (POTRA) domains and a β-barrel membrane domain. We characterized the POTRA domains of BamA from A. baumannii in solution using size-exclusion chromatography small angle X-ray scattering (SEC-SAXS) analysis and determined crystal structures in two conformational states that are drastically different than those previously observed in BamA from other bacteria, indicating that the POTRA domains are even more conformationally dynamic than has been observed previously. Molecular dynamics simulations of the POTRA domains from A. baumannii and Escherichia coli allowed us to identify key structural features that contribute to the observed novel states. Together, these studies expand on our current understanding of the conformational plasticity within BamA across differing bacterial species.

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鲍曼不动杆菌 POTRA 结构域的结构表征揭示了 BamA 的新构象

最近的研究表明，鲍曼不动杆菌（Acinetobacter baumannii）和其他革兰氏阴性病原体引起的感染的一个重要治疗靶点--β-管组装机制（BAM）的核心成分 BamA。同源建模显示，鲍曼不动杆菌中的 BamA 由五个多肽转运相关（POTRA）结构域和一个 β 管膜结构域组成。我们利用尺寸排阻色谱小角 X 射线散射（SEC-SAXS）分析鉴定了鲍曼不动杆菌 BamA 的 POTRA 结构域在溶液中的特征，并确定了两种构象状态下的晶体结构，这两种构象状态与以前在其他细菌的 BamA 中观察到的构象状态截然不同，表明 POTRA 结构域的构象动态性比以前观察到的更强。通过对鲍曼不动杆菌和大肠杆菌的 POTRA 结构域进行分子动力学模拟，我们确定了导致观察到的新状态的关键结构特征。这些研究共同拓展了我们目前对不同细菌物种中 BamA 构象可塑性的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.

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