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Updated: Jun 27, 2026

Interactive Molecular Model Assembly with 3D Printing
Published on: August 13, 2020
Conformational model
Ruth M Risueño1, Angel R Ortiz, Balbino Alarcón
1Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.
Abstract:
The failure to identify changes in the crystal structure of the T-cell antigen receptor (TCR) alpha/beta ectodomains beyond the ligand-binding complementarity-determining region loops is most probably responsible for conformational changes having been relegated to a second plane as a mechanism of signal transduction. However, there is strong biochemical and spectroscopic evidence that the cytoplasmic tails of the tcr and the B-cell antigen receptor undergo conformational changes upon stimulation. This suggests that in the context of the whole TCR complex, including both the TCRalpha/beta ectodomains and the complete CD3 subunits with their transmembrane and cytoplasmic tails, the conformational change has to be transmitted from the ectodomains to the cytoplasmic rails upon ligand binding. While the mechanism of transmission and the importance of conformational changes in T- and B-cell activation are still being elucidated, there are already functional correlates that establish a link between full T-cell activation and this conformational change.
Insights
Conformational changes in T-cell receptor (TCR) cytoplasmic tails, not just ligand-binding regions, are crucial for T-cell activation. This signaling mechanism is vital for immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- Conformational changes in T-cell receptor (TCR) ectodomains beyond ligand-binding loops have been overlooked as a signal transduction mechanism.
- Biochemical and spectroscopic data indicate that cytoplasmic tails of TCR and B-cell antigen receptor (BCR) undergo conformational changes upon stimulation.
Purpose of the Study:
- To investigate the transmission of conformational changes from TCR ectodomains to cytoplasmic tails upon ligand binding.
- To explore the role of these conformational changes in T-cell and B-cell activation.
Main Methods:
- Biochemical assays
- Spectroscopic analysis
- Functional assays linking conformational changes to T-cell activation
Main Results:
- Evidence suggests conformational changes occur in TCR and BCR cytoplasmic tails, not solely in ectodomains.
- Ligand binding to TCR ectodomains likely triggers a transmission of conformational changes to the cytoplasmic tails via CD3 subunits.
- Functional correlates link these conformational changes to full T-cell activation.
Conclusions:
- Conformational changes in the entire TCR complex, including cytoplasmic tails, are critical for signal transduction.
- Understanding the mechanism of transmission and the role of these changes is essential for elucidating T- and B-cell activation pathways.
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