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Paralogous transcription factors (TFs) frequently recognize highly similar DNA motifs. Homodimerization can help distinguish them according to their different dimeric configurations. Here, by studying R2R3-MYB TFs, we show that homodimerization can also directly change the recognized DNA motifs to distinguish between similar TFs. By high-throughput SELEX, we profiled the specificity landscape for 40 R2R3-MYBs of subfamily VIII and curated 833 motif models. The dimeric models show that homodimeric binding has evoked specificity changes for AtMYBs. Focusing on AtMYB2 as an example, we show that homodimerization has modified its specificity and allowed it to recognize additional regulatory sequences that are different from the closely related CCWAA-box AtMYBs and are unique among all AtMYBs. Genomic sites described by the modified dimeric specificities of AtMYB2 are conserved in evolution and involved in AtMYB2-specific transcriptional activation. Collectively, this study provides rich data on sequence preferences of VIII R2R3-MYBs and suggests an alternative mechanism that guides closely related TFs to respective regulatory sites.
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http://dx.doi.org/10.1002/imt2.70009 | DOI Listing |
Biotechnol Lett
September 2025
National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.
Vitreoscilla hemoglobin (VHb), a homodimeric bacterial hemoglobin, exhibits distinct oxygen-binding properties that enhance cellular respiration and metabolic activity, particularly under hypoxic conditions. This review presents an updated and comprehensive synthesis of VHb-related research, encompassing its molecular structure, redox biochemistry, and transcriptional regulation. Compared with previous reviews, this work integrates recent mechanistic insights-especially those concerning transcription factor interactions, redox-coupled electron transfer, and structural-function relationships elucidated via targeted mutagenesis.
View Article and Find Full Text PDFJ Biol Chem
August 2025
Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China; Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, China. Electronic address:
Pseudomonas aeruginosa is an opportunistic pathogen that frequently resides in multispecies communities. During chronic infections, P. aeruginosa employs a diverse arsenal of antibacterial weapons to complete with other bacteria for resources and space.
View Article and Find Full Text PDFACS Chem Biol
August 2025
Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, 130 Scripps Way, Jupiter, Florida 33458, United States.
Fragment-based drug discovery typically relies on specialized spectrometric methods to identify low-affinity compounds that bind to biomolecules. Here, we report a proof-of-concept study on the development of a streamlined fragment-based screening platform for small molecules targeting RNA. This method employs low molecular weight fragments appended with a diazirine reactive moiety and an alkyne tag.
View Article and Find Full Text PDFProtein Sci
September 2025
Faculty of Applied Sciences, Macao Polytechnic University, Macao, China.
Metabotropic glutamate (mGlu) receptors play a crucial role in synaptic transmission through homodimeric or heterodimeric assemblies. Despite their dimeric nature, only one subunit within the mGlu dimer engages with G proteins during activation, and the biased activation can be further controlled by allosteric modulators. Considering the related molecular mechanisms remain elusive, we employed Gaussian accelerated molecular dynamics (GaMD) simulations to investigate the regulated mechanisms in mGlu-mGlu heterodimers.
View Article and Find Full Text PDFRes Sq
August 2025
Department of Biochemistry, 307 Research Dr., Box 3711, Duke University Medical Center, Durham, NC 27710, USA.
DNA damage repair mechanisms are vital for bacterial survival. Recent studies revealed a non-canonical DNA damage response in activated by a WYL-domain transcription factor, DriD. DriD binds ssDNA, produced upon DNA damage, within its WYL-domain, and drives expression at multiple promoters.
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