小柯机器人

比利时VIB-VUB结构生物学中心Han Remaut团队近期取得重要工作进展，他们研究提出，SlyB将外膜蛋白封装在应激诱导的脂质纳米结构域中。相关研究成果2023年12月11日在线发表于《自然》杂志上。

据介绍，革兰氏阴性菌的外膜（OM）由一个不对称的磷脂-脂多糖双分子层组成，双分子层紧密地包裹着β-桶蛋白（OMP）和脂蛋白。这种双分子层的结构和组成受到密切监测，对细胞的完整性和存活至关重要。

研究人员发现PhoPQ应激调节子中的脂蛋白SlyB与外膜蛋白质组形成稳定的应激诱导复合物。SlyB由10kDa周质β-三明治结构域和甘氨酸拉链结构域组成，该结构域形成具有离散磷脂和脂多糖结合位点的跨膜α-螺旋发夹。在脂质不对称性丧失后，SlyB寡聚成环状跨膜复合物，将β-桶蛋白封装到大小可变的脂质纳米结构域中。研究人员发现SlyB纳米结构域的形成，在LPS被抗微生物肽或急性阳离子短缺破坏稳定过程中是至关重要的，在缺乏功能性SlyB的情况下，这种情况会导致OMP的损失和OM屏障功能的损害。

总之，这一数据揭示了SlyB是一种参与细胞包膜蛋白稳定和完整性的区室化跨膜保护蛋白，并表明SlyB代表了一个更大的广泛保守（脂）蛋白家族，具有能够形成脂质纳米结构域的2TM甘氨酸拉链结构域。

附：英文原文

Title: SlyB encapsulates outer membrane proteins in stress-induced lipid nanodomains

Author: Janssens, Arne, Nguyen, Van Son, Cecil, Adam J., Van der Verren, Sander E., Timmerman, Evy, Deghelt, Michal, Pak, Alexander J., Collet, Jean-Franois, Impens, Francis, Remaut, Han

Issue&Volume: 2023-12-11

Abstract: The outer membrane (OM) in Gram-negative bacteria consists of an asymmetric phospholipid – lipopolysaccharide bilayer densely packed with β-barrel proteins (OMPs) and lipoproteins1. The architecture and composition of this bilayer is closely monitored and essential to cell integrity and survival2-4. Here we find that SlyB, a lipoprotein in the PhoPQ stress regulon forms stable stress-induced complexes with the outer membrane proteome. SlyB consists of a 10 kDa periplasmic β-sandwich domain and a glycine zipper domain that forms a transmembrane α-helical hairpin with a discrete phospholipid and lipopolysaccharide binding sites. Upon loss in lipid asymmetry, SlyB oligomerizes into ring-shaped transmembrane complexes that encapsulate β-barrel proteins into lipid nanodomains of variable size. We find SlyB nanodomain formation is essential during LPS destabilization by antimicrobial peptides or acute cation shortage, conditions that result in a loss of OMPs and compromised OM barrier function in absence of a functional SlyB. Our data reveal SlyB as a compartmentalizing transmembrane guard protein involved in cell envelope proteostasis and integrity, and suggest SlyB represents a larger family of broadly conserved (lipo)proteins with 2TM glycine zipper domains capable of forming lipid nanodomains.

DOI: 10.1038/s41586-023-06925-5

Source: https://www.nature.com/articles/s41586-023-06925-5

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