A major unanswered question is how a TCR discriminates between foreign and self-peptides presented on the APC surface. Here, we used in situ fluorescence resonance energy transfer (FRET) to measure the distances of single TCR-pMHC bonds and the conformations of individual TCR-CD3ζ receptors at the membranes of live primary T cells. We found that a TCR discriminates between closely related peptides by forming single TCR-pMHC bonds with different conformations, and the most potent pMHC forms the shortest bond. The bond conformation is an intrinsic property that is independent of the binding affinity and kinetics, TCR microcluster formation, and CD4 binding. The bond conformation dictates the degree of CD3ζ dissociation from the inner leaflet of the plasma membrane via a positive calcium signaling feedback loop to precisely control the accessibility of CD3ζ ITAMs for phosphorylation. Our data revealed the mechanism by which a TCR deciphers the structural differences among peptides via the TCR-pMHC bond conformation.
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http://dx.doi.org/10.1038/s41423-019-0273-6 | DOI Listing |
J Am Chem Soc
January 2025
Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.
Chemical selectivity is traditionally understood in the context of rigid molecular scaffolds with precisely defined local coordination and chemical environments that ultimately facilitate a given transformation of interest. By contrast, nature leverages dynamic structures and strong coupling to enable specific interactions with target species in otherwise complex media. Taking inspiration from nature, we demonstrate unconventional selectivity in the solvent extraction of light over heavy lanthanides using a conformationally flexible ligand called octadecyl acyclopa (ODA).
View Article and Find Full Text PDFSAR QSAR Environ Res
January 2025
Research and Scientific Studies Unit, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia.
Ras is identified as a human oncogene which is frequently mutated in human cancers. Among its three isoforms (K, N, and H), KRas is the most frequently mutated. Mutant Ras exhibits reduced GTPase activity, leading to the prolonged activation of its conformation.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, PR China. Electronic address:
Botrytis cinerea populations resistant to succinate dehydrogenase inhibitors (SDHIs) represent a major problem for the sustainable development of modern agriculture. In the present study, the resistance mechanism of B_P225F and B_H272R mutations in B. cinerea SDH (BcSDH) resistant to SDHIs fungicides, including boscalid (BOS), penflufen (PEN), pydiflumetofen (PYD), fluopyram (FLU), and benzovindiflupyr (BEN), was uncovered.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
College of Food Science and Engineering, Inner Mongolia Agricultural University, China.
This study investigated β-glucan with diverse conformations by using molecular dynamics simulations to analyze their conformational transitions in water. Stable conformations were docked with the Dectin-1 protein to evaluate key metrics such as favorable conformations, root-mean-square deviation, hydrogen bond interactions, and their effects on macrophage activity. Results revealed that single-chain β-1,3-glucan with a degree of polymerization (DP) of 24 forms aggregates in water, while triple-chain β-1,3-glucan with a DP of 6 tends to form double helices.
View Article and Find Full Text PDFBiophys Chem
December 2024
Department of Chemistry, De La Salle University, Manila 0922, Philippines. Electronic address:
SARS-CoV-2 remains a global threat with new sublineages posing challenges, particularly in the Philippines. Hesperidin (HD) is being studied as a potential prophylactic for COVID-19. However, the virus's rapid evolution could alter how HD binds to it, affecting its effectiveness.
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