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Yorodumi- PDB-7zqs: Cryo-EM Structure of Human Transferrin Receptor 1 bound to DNA Aptamer -
+Open data
-Basic information
Entry | Database: PDB / ID: 7zqs | ||||||
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Title | Cryo-EM Structure of Human Transferrin Receptor 1 bound to DNA Aptamer | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / CD71 / Transmembrane Glycoprotein | ||||||
Function / homology | Function and homology information transferrin receptor activity / negative regulation of mitochondrial fusion / transferrin transport / Transferrin endocytosis and recycling / positive regulation of isotype switching / response to iron ion / response to copper ion / response to manganese ion / RND1 GTPase cycle / RND2 GTPase cycle ...transferrin receptor activity / negative regulation of mitochondrial fusion / transferrin transport / Transferrin endocytosis and recycling / positive regulation of isotype switching / response to iron ion / response to copper ion / response to manganese ion / RND1 GTPase cycle / RND2 GTPase cycle / RHOB GTPase cycle / Golgi Associated Vesicle Biogenesis / RHOJ GTPase cycle / RHOC GTPase cycle / RHOQ GTPase cycle / RHOH GTPase cycle / CDC42 GTPase cycle / transport across blood-brain barrier / RHOG GTPase cycle / RHOA GTPase cycle / RAC2 GTPase cycle / RAC3 GTPase cycle / positive regulation of bone resorption / response to retinoic acid / positive regulation of B cell proliferation / clathrin-coated pit / Hsp70 protein binding / positive regulation of T cell proliferation / RAC1 GTPase cycle / cellular response to leukemia inhibitory factor / osteoclast differentiation / response to nutrient / acute-phase response / positive regulation of protein-containing complex assembly / clathrin-coated endocytic vesicle membrane / HFE-transferrin receptor complex / receptor internalization / recycling endosome / positive regulation of protein localization to nucleus / recycling endosome membrane / extracellular vesicle / melanosome / cellular response to xenobiotic stimulus / Cargo recognition for clathrin-mediated endocytosis / double-stranded RNA binding / virus receptor activity / positive regulation of peptidyl-serine phosphorylation / Clathrin-mediated endocytosis / positive regulation of NF-kappaB transcription factor activity / iron ion transport / cytoplasmic vesicle / basolateral plasma membrane / positive regulation of canonical NF-kappaB signal transduction / blood microparticle / intracellular iron ion homeostasis / response to hypoxia / early endosome / endosome membrane / endosome / intracellular signal transduction / positive regulation of protein phosphorylation / external side of plasma membrane / intracellular membrane-bounded organelle / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / protein kinase binding / perinuclear region of cytoplasm / cell surface / protein homodimerization activity / extracellular space / RNA binding / extracellular exosome / extracellular region / membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) unidentified (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.54 Å | ||||||
Authors | Bansia, H. / Wang, T. / Gutierrez, D. / des Georges, A. | ||||||
Funding support | United States, 1items
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Citation | Journal: J Am Chem Soc / Year: 2022 Title: Discovery of a Transferrin Receptor 1-Binding Aptamer and Its Application in Cancer Cell Depletion for Adoptive T-Cell Therapy Manufacturing. Authors: Emmeline L Cheng / Ian I Cardle / Nataly Kacherovsky / Harsh Bansia / Tong Wang / Yunshi Zhou / Jai Raman / Albert Yen / Dominique Gutierrez / Stephen J Salipante / Amédée des Georges / ...Authors: Emmeline L Cheng / Ian I Cardle / Nataly Kacherovsky / Harsh Bansia / Tong Wang / Yunshi Zhou / Jai Raman / Albert Yen / Dominique Gutierrez / Stephen J Salipante / Amédée des Georges / Michael C Jensen / Suzie H Pun / Abstract: The clinical manufacturing of chimeric antigen receptor (CAR) T cells includes cell selection, activation, gene transduction, and expansion. While the method of T-cell selection varies across ...The clinical manufacturing of chimeric antigen receptor (CAR) T cells includes cell selection, activation, gene transduction, and expansion. While the method of T-cell selection varies across companies, current methods do not actively eliminate the cancer cells in the patient's apheresis product from the healthy immune cells. Alarmingly, it has been found that transduction of a single leukemic B cell with the CAR gene can confer resistance to CAR T-cell therapy and lead to treatment failure. In this study, we report the identification of a novel high-affinity DNA aptamer, termed tJBA8.1, that binds transferrin receptor 1 (TfR1), a receptor broadly upregulated by cancer cells. Using competition assays, high resolution cryo-EM, and model building of the aptamer into the resulting electron density, we reveal that tJBA8.1 shares a binding site on TfR1 with holo-transferrin, the natural ligand of TfR1. We use tJBA8.1 to effectively deplete B lymphoma cells spiked into peripheral blood mononuclear cells with minimal impact on the healthy immune cell composition. Lastly, we present opportunities for affinity improvement of tJBA8.1. As TfR1 expression is broadly upregulated in many cancers, including difficult-to-treat T-cell leukemias and lymphomas, our work provides a facile, universal, and inexpensive approach for comprehensively removing cancerous cells from patient apheresis products for safe manufacturing of adoptive T-cell therapies. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7zqs.cif.gz | 264.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7zqs.ent.gz | 206 KB | Display | PDB format |
PDBx/mmJSON format | 7zqs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zq/7zqs ftp://data.pdbj.org/pub/pdb/validation_reports/zq/7zqs | HTTPS FTP |
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-Related structure data
Related structure data | 14874MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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