Structural modeling and characterization of the Mycobacterium tuberculosis MmpL3 C-terminal domain.

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Naomi Berkowitz, Allison MacMillan, Marit B Simmons, Ujwal Shinde, Georgiana E Purdy
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引用次数: 0

Abstract

The Mycobacterium tuberculosis (Mtb) cell envelope provides a protective barrier against the immune response and antibiotics. The mycobacterial membrane protein large (MmpL) family of proteins export cell envelope lipids and siderophores; therefore, these proteins are important for the basic biology and pathogenicity of Mtb. In particular, MmpL3 is essential and a known drug target. Despite interest in MmpL3, the structural data in the field are incomplete. Utilizing homology modeling, AlphaFold, and biophysical techniques, we characterized the cytoplasmic C-terminal domain (CTD) of MmpL3 to better understand its structure and function. Our in silico models of the MmpL11TB and MmpL3TB CTD reveal notable features including a long unstructured linker that connects the globular domain to the last transmembrane (TM) in each transporter, charged lysine and arginine residues facing the membrane, and a C-terminal alpha helix. Our predicted overall structure enables a better understanding of these transporters.

结核分枝杆菌 MmpL3 C 端结构域的结构建模和特征描述。
结核分枝杆菌(Mtb)的细胞包膜是抵御免疫反应和抗生素的保护屏障。分枝杆菌膜蛋白大分子(MmpL)家族的蛋白质可输出细胞包膜脂质和苷元;因此,这些蛋白质对 Mtb 的基础生物学和致病性非常重要。特别是,MmpL3 是一种重要的已知药物靶标。尽管人们对 MmpL3 很感兴趣,但该领域的结构数据并不完整。利用同源建模、AlphaFold 和生物物理技术,我们对 MmpL3 的细胞质 C 端结构域(CTD)进行了表征,以更好地了解其结构和功能。我们建立的 MmpL11TB 和 MmpL3TB CTD 的硅学模型揭示了一些显著特点,包括连接球状结构域和每个转运体的最后一个跨膜 (TM) 的非结构化长连接物、面向膜的带电赖氨酸和精氨酸残基以及一个 C 端阿尔法螺旋。我们预测的整体结构有助于更好地了解这些转运体。
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
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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