Two-component systems (TCS) are short signalling pathways generally occurring in prokaryotes. They frequently regulate prokaryotic stimulus responses and thus are also of interest for engineering in biotechnology and synthetic biology. The aim of this study is to better understand and describe rewiring of TCS while investigating different evolutionary scenarios. Based on large-scale screens of TCS in different organisms, this study gives detailed data, concrete alignments, and structure analysis on three general modification scenarios, where TCS were rewired for new responses and functions: (i) exchanges in the sequence within single TCS domains, (ii) exchange of whole TCS domains; (iii) addition of new components modulating TCS function. As a result, the replacement of stimulus and promotor cassettes to rewire TCS is well defined exploiting the alignments given here. The diverged TCS examples are non-trivial and the design is challenging. Designed connector proteins may also be useful to modify TCS in selected cases.
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http://dx.doi.org/10.4137/BBI.S9356 | DOI Listing |
Hum Genet
January 2025
TCS Research, Tata Consultancy Services, Hyderabad, India.
Variants of uncertain significance (VUS) represent variants that lack sufficient evidence to be confidently associated with a disease, thus posing a challenge in the interpretation of genetic testing results. Here we report an improved method for predicting the VUS of Arylsulfatase A (ARSA) gene as part of the Critical Assessment of Genome Interpretation challenge (CAGI6). Our method uses a transfer learning approach that leverages a pre-trained protein language model to predict the impact of mutations on the activity of the ARSA enzyme, whose deficiency is known to cause a rare genetic disorder, metachromatic leukodystrophy.
View Article and Find Full Text PDFJ Bacteriol
January 2025
Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, Wisconsin, USA.
Unlabelled: has numerous two-component signaling systems (TCSs), many of which regulate the complex social behaviors of this soil bacterium. A subset of TCSs consists of NtrC-like response regulators (RRs) and their cognate histidine sensor kinases (SKs). We have previously demonstrated that a multi-component, phosphorelay TCS named NmpRSTU plays a role in social motility.
View Article and Find Full Text PDFJ Hazard Mater
January 2025
Marine Synthetic Ecology Research Center, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Marine Science, Sun Yat-sen University, Zhuhai 519080, China. Electronic address:
The polychlorinated aromatic antimicrobial agent triclosan (TCS) is widely used to indiscriminately and rapidly kill microorganisms. The global use of TCS has led to widespread environmental contamination, posing significant threats to ecosystem and human health. Here we reported a newly isolated Pseudomonas sp.
View Article and Find Full Text PDFInt J Med Inform
January 2025
School of Computer Science and Engineering, Hubei Key Laboratory of Intelligent Robot, Wuhan Institute of Technology, Wuhan, PR China. Electronic address:
Background: In the context of routine breast cancer diagnosis, the precise discrimination between benign and malignant breast masses holds utmost significance. Notably, few prior investigations have concurrently explored the integration of imaging histology features, deep learning characteristics, and clinical parameters. The primary objective of this retrospective study was to pioneer a multimodal feature fusion model tailored for the prediction of breast tumor malignancy, harnessing the potential of ultrasound images.
View Article and Find Full Text PDFLife (Basel)
January 2025
School of Environment and Geography, Qingdao University, Qingdao 266071, China.
The potential health risks posed by the coexistence of nanoplastics (NPs) and triclosan (TCS) have garnered significant attention. However, the effects and underlying mechanisms of NPs and TCS on key functional proteins at the molecular level remain poorly understood. This study reports the effect of polystyrene nanoplastics (PSNPs) on the binding of TCS to human serum albumin (HSA) using multispectral methods and molecular simulation systems.
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