Mycobacterium tuberculosis TtfA is a Highly Stable Membrane-Anchored DNA-Binding Protein.

IF 2.3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Membrane Biology Pub Date : 2025-06-26 DOI:10.1007/s00232-025-00352-5

Saksham Jain, Akanksha Gajanan Patil, Saniya Patil, Raju Mukherjee, Vikas Jain, Radhakrishnan Mahalakshmi

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Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a deadly intracellular pathogen, with a persistent infectivity and high morbidity rate. Mtb has successfully evaded drugs and modern antibiotics, while also developing resistance and adaptability. To obtain newer avenues for therapeutics against Mtb, we proposed to identify and characterize membrane proteins of Mtb. To this end, we report the successful characterization of the locus rv0383c, which codes for a 284-residue membrane-anchored protein. We show that the protein product, named TtfA, possesses an N-terminal transmembrane helix, a low complexity region, an α + β central region, and a C-terminally highly unstructured region. Our studies reveal that the extramembranous domain possesses non-specific DNA-binding ability. Additionally, TtfA folds into a highly stable structure that resists thermal unfolding. TtfA is selectively sensitive to the surrounding pH. The promising outcomes we obtain with TtfA as one of the next-generation antibiotic targets against Mtb can pave the way for characterizing other membrane proteins toward finding long-term cures for this endemic disease.

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结核分枝杆菌TtfA是一种高度稳定的膜锚定dna结合蛋白。

结核分枝杆菌（Mycobacterium tuberculosis, Mtb）是一种致死性细胞内病原体，具有持续传染性和高发病率。结核分枝杆菌成功地避开了药物和现代抗生素，同时也产生了耐药性和适应性。为了获得治疗结核分枝杆菌的新途径，我们提出鉴定和表征结核分枝杆菌的膜蛋白。为此，我们报道了基因座rv0383c的成功鉴定，该基因座编码284个残基膜锚定蛋白。结果表明，该蛋白产物TtfA具有一个n端跨膜螺旋、一个低复杂性区域、一个α + β中心区域和一个c端高度非结构化区域。我们的研究表明，膜外结构域具有非特异性的dna结合能力。此外，TtfA折叠成一种高度稳定的结构，可以抵抗热展开。TtfA对周围ph值具有选择性敏感性。我们将TtfA作为下一代Mtb抗生素靶点之一获得的有希望的结果可以为表征其他膜蛋白以寻找这种地方病的长期治疗方法铺平道路。

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

Journal of Membrane Biology 生物-生化与分子生物学

CiteScore

4.80

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.