ArticleNature communications2025
The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- The Y105 phosphosite between the SH3.1 and SH3.2 domains of Nck1 regulates its binding to CD3ϵ.iScience · 2026Article
- Engineering a Second Interchain Disulfide Bond in the αβ T-Cell Receptor Constant Domain: A Powerful Strategy to Enhance Stability, Pairing Fidelity, and Therapeutic Efficacy in TCR-T Cell Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Leveraging mathematical models to predict and control T-cell activation.PLoS computational biology · 2026Article
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Atomistic TCR-ligand interactions instruct memory T-cell differentiation.bioRxiv : the preprint server for biology · 2025Article
- CAR-engineered lymphocyte persistence is governed by a FAS ligand-FAS autoregulatory circuit.Nature cancer · 2025Article
- Nanodiscs remain indispensable for Cryo-EM studies of membrane proteins.Current opinion in structural biology · 2025Review
- The Structural Biology of T-Cell Antigen Detection at Close Contacts.Immunological reviews · 2025Review
- TCR catch bonds nonlinearly control CD8 cooperation to shape T cell specificity.Cell research · 2025Article
- Biophysical and Structural Features of αβT-Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T-Cell Activation.Immunological reviews · 2025Review
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- The recent advancement of TCR-T cell therapies for cancer treatment.Acta biochimica et biophysica Sinica · 2024Review
- T-cell virtuosity in ''knowing thyself".Frontiers in immunology · 2024Review
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Abstract
The T-cell receptor (TCR) initiates T-lymphocyte activation, but the mechanism of TCR activation remains uncertain. Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte antigen (HLA)-bound human TCR-CD3 complex in nanodiscs that provide a native-like lipid environment. Distinct from the open and extended conformation seen in detergent, the unliganded TCR-CD3 in nanodiscs adopts two related closed and compacted conformations that represent its physiologic resting state in vivo. By contrast, the HLA-bound complex adopts the open and extended conformation, and conformation-locking disulfide mutants show that ectodomain opening is necessary for maximal ligand-dependent T-cell activation. These structures also reveal conformation-dependent protein-lipid and glycan-glycan interactions within the TCR. Together, these results establish allosteric conformational change during TCR activation, reveal avenues for immunotherapeutic engineering, and highlight the importance of native-like lipid environments for membrane protein structure determination.
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