The Structural Features of MlaD Illuminate its Unique Ligand-Transporting Mechanism and Ancestry

IF 1.9 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Angshu Dutta, Shankar Prasad Kanaujia
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引用次数: 0

Abstract

The membrane-associated solute-binding protein (SBP) MlaD of the maintenance of lipid asymmetry (Mla) system has been reported to help the transport of phospholipids (PLs) between the outer and inner membranes of Gram-negative bacteria. Despite the availability of structural information, the molecular mechanism underlying the transport of PLs and the ancestry of the protein MlaD remain unclear. In this study, we report the crystal structures of the periplasmic region of MlaD from Escherichia coli (EcMlaD) at a resolution range of 2.3–3.2 Å. The EcMlaD protomer consists of two distinct regions, viz. N-terminal β-barrel fold consisting of seven strands (referred to as MlaD domain) and C-terminal α-helical domain (HD). The protein EcMlaD oligomerizes to give rise to a homo-hexameric ring with a central channel that is hydrophobic and continuous with a variable diameter. Interestingly, the structural analysis revealed that the HD, instead of the MlaD domain, plays a critical role in determining the oligomeric state of the protein. Based on the analysis of available structural information, we propose a working mechanism of PL transport, viz. “asymmetric protomer movement (APM)”. Wherein half of the EcMlaD hexamer would rise in the periplasmic side along with an outward movement of pore loops, resulting in the change of the central channel geometry. Furthermore, this study highlights that, unlike typical SBPs, EcMlaD possesses a fold similar to EF/AMT-type beta(6)-barrel and a unique ancestry. Altogether, the findings firmly establish EcMlaD to be a non-canonical SBP with a unique ligand-transport mechanism.

Abstract Image

MlaD 的结构特征揭示了其独特的配体传输机制和祖先。
据报道,维持脂质不对称(Mla)系统中的膜相关溶质结合蛋白(SBP)MlaD有助于磷脂(PLs)在革兰氏阴性细菌外膜和内膜之间的转运。尽管已有结构信息,但磷脂转运的分子机制和蛋白 MlaD 的起源仍不清楚。在这项研究中,我们报告了大肠杆菌 MlaD(EcMlaD)质外区域的晶体结构,其分辨率范围为 2.3-3.2 Å。EcMlaD 的原体由两个不同的区域组成,即 N 端由七条链组成的β-桶状折叠(称为 MlaD 结构域)和 C 端的α-螺旋结构域(HD)。蛋白 EcMlaD 通过寡聚形成一个同六聚体环,其中央通道疏水且连续,直径可变。有趣的是,结构分析表明,HD 而不是 MlaD 结构域在决定蛋白质的寡聚状态方面起着关键作用。根据对现有结构信息的分析,我们提出了一种 PL 运输的工作机制,即 "不对称原体运动(APM)"。在这一机制中,EcMlaD 六聚体的一半会随着孔环的向外运动而上升到外质侧,从而导致中央通道的几何形状发生变化。此外,这项研究还强调,与典型的 SBPs 不同,EcMlaD 具有类似于 EF/AMT 型 beta(6)-barrel 的折叠和独特的祖先。总之,这些发现有力地证明了 EcMlaD 是一种非典型 SBP,具有独特的配体转运机制。
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
The Protein Journal
The Protein Journal 生物-生化与分子生物学
CiteScore
5.20
自引率
0.00%
发文量
57
审稿时长
12 months
期刊介绍: The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.
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