tRNA threonylcarbamoyladenosine metabolic process / regulation of lymphocyte apoptotic process / Fc-gamma receptor III complex / Fc-gamma receptor signaling pathway / gamma-delta T cell activation / positive regulation of cell-cell adhesion mediated by integrin / positive thymic T cell selection / signal complex assembly / Nef and signal transduction / positive regulation of cell-matrix adhesion ...tRNA threonylcarbamoyladenosine metabolic process / regulation of lymphocyte apoptotic process / Fc-gamma receptor III complex / Fc-gamma receptor signaling pathway / gamma-delta T cell activation / positive regulation of cell-cell adhesion mediated by integrin / positive thymic T cell selection / signal complex assembly / Nef and signal transduction / positive regulation of cell-matrix adhesion / alpha-beta T cell receptor complex / T cell receptor complex / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / dendrite development / alpha-beta T cell activation / establishment or maintenance of cell polarity / Generation of second messenger molecules / FCGR activation / protein complex oligomerization / immunological synapse / Co-inhibition by PD-1 / cerebellum development / Role of phospholipids in phagocytosis / antigen processing and presentation of peptide antigen via MHC class I / T cell receptor binding / positive regulation of T cell proliferation / FCGR3A-mediated IL10 synthesis / cell surface receptor protein tyrosine kinase signaling pathway / protein tyrosine kinase binding / regulation of natural killer cell mediated immunity / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / Endosomal/Vacuolar pathway / T cell activation / FCGR3A-mediated phagocytosis / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / regulation of iron ion transport / negative regulation of iron ion transport / negative regulation of forebrain neuron differentiation / antigen processing and presentation of exogenous peptide antigen via MHC class Ib / peptide antigen assembly with MHC class I protein complex / clathrin-coated endocytic vesicle membrane / ER to Golgi transport vesicle membrane / HFE-transferrin receptor complex / MHC class I peptide loading complex / transferrin transport / negative regulation of receptor-mediated endocytosis / cellular response to iron ion / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / peptide antigen assembly with MHC class II protein complex / MHC class I protein complex / SH3 domain binding / negative regulation of epithelial cell proliferation / Regulation of actin dynamics for phagocytic cup formation / cellular response to nicotine / negative regulation of neurogenesis / positive regulation of receptor-mediated endocytosis / MHC class II protein complex / specific granule lumen / positive regulation of immune response / antigen processing and presentation of exogenous peptide antigen via MHC class II / peptide antigen binding / T cell receptor signaling pathway / recycling endosome membrane / phagocytic vesicle membrane / positive regulation of T cell activation / Interferon gamma signaling / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / cell-cell junction / sensory perception of smell / Modulation by Mtb of host immune system / tertiary granule lumen / positive regulation of cellular senescence / MHC class II protein complex binding / DAP12 signaling / transmembrane signaling receptor activity / Downstream TCR signaling / late endosome membrane / Cargo recognition for clathrin-mediated endocytosis / protein transport / Clathrin-mediated endocytosis / signaling receptor complex adaptor activity / ER-Phagosome pathway / protein-containing complex assembly / cell body / early endosome membrane / amyloid fibril formation / protein homotetramerization / dendritic spine / adaptive immune response / regulation of apoptotic process / intracellular iron ion homeostasis / learning or memory / protein-macromolecule adaptor activity / cell surface receptor signaling pathway / immune response Similarity search - Function
National Institutes of Health/National Cancer Institute (NIH/NCI)
T32CA9207
United States
National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS)
KL2TR001865
United States
National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS)
UL1TR001866
United States
Other private
Black Family Metastasis Center
Shapiro-Silverberg Fund for the Advancement of Translational Research
United States
The Mark Foundation
Walz-Notti Aspire
United States
Citation
Journal: bioRxiv / Year: 2024 Title: The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex. Authors: Ryan Q Notti / Fei Yi / Søren Heissel / Martin W Bush / Zaki Molvi / Pujita Das / Henrik Molina / Christopher A Klebanoff / Thomas Walz Abstract: The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( ). Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte ...The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( ). 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 . 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. Together, these results reveal allosteric conformational change during TCR activation and highlight the importance of native-like lipid environments for membrane protein structure determination.
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