An investigation of the interactions of two novel and several known DBTAA-adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA-propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure-activity relation for the studied series of compounds showed that the essential structural features for the ICD recognition are a) the presence of DNA-binding appendages (adenine side chain and positively charged side chain) on both DBTAA side chains, and b) the presence of a short propyl linker, which does not support intramolecular aromatic stacking between DBTAA and adenine. The observed AT-DNA-ICD pattern differs from previously reported ss-DNA (poly dT) ICD recognition by a strong negative ICD band at 350 nm, which allows for the dynamic differentiation between ss-DNA (poly dT) and coupled ds-AT-DNA.
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http://dx.doi.org/10.3762/bjoc.10.225 | DOI Listing |
Biomol NMR Assign
January 2025
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA.
The nutrient germinant receptors (GRs) in spores of Bacillus species consist of a cluster of three proteins- designated A, B, and C subunits- that play a critical role in initiating the germination of dormant spores in response to specific nutrient molecules. The Bacillus cereus GerI GR is essential for inosine-induced germination; however, the roles of the individual subunits and the mechanism by which germinant binding activates GR function remain unclear. In this study, we report the backbone chemical shift assignments of the N-terminal domain (NTD) of the A subunit of GerI (GerIA).
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Division of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Cholesterol plays a pivotal role in modulating the activity of mechanistic target of rapamycin complex 1 (mTOR1), thereby regulating cell growth and metabolic homeostasis. LYCHOS, a lysosome-localized G-protein-coupled receptor-like protein, emerges as a cholesterol sensor and is capable of transducing the cholesterol signal to affect the mTORC1 function. However, the precise mechanism by which LYCHOS recognizes cholesterol remains unknown.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.
View Article and Find Full Text PDFAnal Chem
January 2025
School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, P. R. China.
Tumor-derived extracellular vesicles (T-EVs) PD-L1 are an important biomarker for predicting immunotherapy response and can help us understand the mechanism of resistance to immunotherapy. However, this is due to the interference from a large proportion of nontumor-derived EVs. It is still challenging to accurately analyze T-EVs PD-L1 in complex human fluids.
View Article and Find Full Text PDFFish Shellfish Immunol
January 2025
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, School of Marine Sciences, Ningbo University, Ningbo 315211, P.R. China; Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Meishan Campus, Ningbo University, Ningbo 315832, China; Key Laboratory of Aquacultural Biotechnology of Ministry of Education, Ningbo University, Ningbo 315211, P.R. China. Electronic address:
The liver-expressed antimicrobial peptide 2 (LEAP2) is gaining recognition for its immune regulatory functions beyond direct antimicrobial activity. In this study, we investigated the role of mudskipper (Boleophthalmus pectinirostris) LEAP2 (BpLEAP2) in enhancing the survival, gut health, and immune resilience against Edwardsiella tarda infection. Pre-oral delivery of BpLEAP2 significantly improved survival rates and mitigated infection-induced damage to the gut, as evidenced by preserved villus length and goblet cell count.
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