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具有不同功能和系统发育分布的三个细菌DedA亚家族。

Three bacterial DedA subfamilies with distinct functions and phylogenetic distribution.

作者信息

Todor Horia, Herrera Nadia, Gross Carol

机构信息

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.

Lead Contact.

出版信息

bioRxiv. 2023 Jan 5:2023.01.04.522824. doi: 10.1101/2023.01.04.522824.

DOI:10.1101/2023.01.04.522824
PMID:36712119
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9881974/
Abstract

UNLABELLED

Recent studies in bacteria suggested that the broadly conserved but enigmatic DedA proteins function as undecaprenyl-phosphate (UndP) flippases, recycling this essential lipid carrier. To determine whether all DedA proteins have UndP flippase activity, we performed a phylogenetic analysis and correlated it to previously published experimental results and predicted structures. We uncovered three major DedA subfamilies: one contains UndP flippases, the second contains putative phospholipid flippases and is associated with aerobic metabolism, and the third is found only in specific Gram-negative phyla.

IMPORTANCE

DedA-family proteins are highly conserved and nearly ubiquitous integral membrane proteins found in Archaea, Bacteria, and Eukaryotes. Recent work revealed that eukaryotic DedA proteins are phospholipid scramblases and some bacterial DedA proteins are undecaprenyl phosphate flippases. We perform a phylogenetic analysis of this protein family in Bacteria revealing 3 DedA subfamilies with distinct phylogenetic distributions, genomic contexts, and putative functions. Our analysis lays the groundwork for a deeper understanding of DedA proteins and their role in maintaining and modifying the membrane.

摘要

未标记

最近在细菌中的研究表明,广泛保守但神秘的DedA蛋白作为磷酸十一异戊烯酯(UndP)翻转酶发挥作用,循环利用这种必需的脂质载体。为了确定所有DedA蛋白是否都具有UndP翻转酶活性,我们进行了系统发育分析,并将其与先前发表的实验结果和预测结构相关联。我们发现了三个主要的DedA亚家族:一个包含UndP翻转酶,第二个包含推定的磷脂翻转酶并与有氧代谢相关,第三个仅存在于特定的革兰氏阴性菌门中。

重要性

DedA家族蛋白是在古细菌、细菌和真核生物中发现的高度保守且几乎普遍存在的整合膜蛋白。最近的研究表明,真核生物的DedA蛋白是磷脂翻转酶,一些细菌的DedA蛋白是磷酸十一异戊烯酯翻转酶。我们对细菌中的这个蛋白家族进行了系统发育分析,揭示了具有不同系统发育分布、基因组背景和推定功能的3个DedA亚家族。我们的分析为更深入了解DedA蛋白及其在维持和修饰膜中的作用奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/517f/9881974/94dcac1ef6fb/nihpp-2023.01.04.522824v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/517f/9881974/6969a27eaf33/nihpp-2023.01.04.522824v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/517f/9881974/94dcac1ef6fb/nihpp-2023.01.04.522824v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/517f/9881974/6969a27eaf33/nihpp-2023.01.04.522824v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/517f/9881974/94dcac1ef6fb/nihpp-2023.01.04.522824v1-f0003.jpg

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本文引用的文献

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Two broadly conserved families of polyprenyl-phosphate transporters.两类广泛保守的多萜醇磷酸载体家族。
Nature. 2023 Jan;613(7945):729-734. doi: 10.1038/s41586-022-05587-z. Epub 2022 Nov 30.
2
Undecaprenyl phosphate translocases confer conditional microbial fitness.十一烯基磷酸转位酶赋予微生物条件适应性。
Nature. 2023 Jan;613(7945):721-728. doi: 10.1038/s41586-022-05569-1. Epub 2022 Nov 30.
3
A Klebsiella pneumoniae DedA family membrane protein is required for colistin resistance and for virulence in wax moth larvae.
一种肺炎克雷伯菌 DedA 家族膜蛋白对多粘菌素耐药性和黄粉虫幼虫毒力是必需的。
Sci Rep. 2021 Dec 21;11(1):24365. doi: 10.1038/s41598-021-03834-3.
4
A DedA Family Membrane Protein in Indium Extrusion in sp. B2A1Ga4.sp. B2A1Ga4中一种参与铟排出的DedA家族膜蛋白。
Front Microbiol. 2021 Nov 26;12:772127. doi: 10.3389/fmicb.2021.772127. eCollection 2021.
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Topological analysis of a bacterial DedA protein associated with alkaline tolerance and antimicrobial resistance.拓扑分析一种与碱性耐受和抗菌耐药性相关的细菌 DedA 蛋白。
Microbiology (Reading). 2021 Dec;167(12). doi: 10.1099/mic.0.001125.
6
YhdP, TamB, and YdbH Are Redundant but Essential for Growth and Lipid Homeostasis of the Gram-Negative Outer Membrane. YhdP、TamB 和 YdbH 对于革兰氏阴性外膜的生长和脂质稳态是冗余但必需的。
mBio. 2021 Dec 21;12(6):e0271421. doi: 10.1128/mBio.02714-21. Epub 2021 Nov 16.
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Highly accurate protein structure prediction with AlphaFold.利用 AlphaFold 进行高精度蛋白质结构预测。
Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
8
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Appl Environ Microbiol. 2021 Aug 26;87(18):e0091521. doi: 10.1128/AEM.00915-21.
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A link between pH homeostasis and colistin resistance in bacteria.pH 值稳态与细菌中介导黏菌素耐药性的关联。
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