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- PDB-7zqs: Cryo-EM Structure of Human Transferrin Receptor 1 bound to DNA Aptamer -
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Basic information
Entry | Database: PDB / ID: 7zqs | ||||||
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Title | Cryo-EM Structure of Human Transferrin Receptor 1 bound to DNA Aptamer | ||||||
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![]() | MEMBRANE PROTEIN / CD71 / Transmembrane Glycoprotein | ||||||
Function / homology | ![]() transferrin receptor activity / negative regulation of mitochondrial fusion / transferrin transport / Transferrin endocytosis and recycling / positive regulation of isotype switching / Differentiation of keratinocytes in interfollicular epidermis in mammalian skin / response to copper ion / response to iron ion / RND1 GTPase cycle / response to manganese ion ...transferrin receptor activity / negative regulation of mitochondrial fusion / transferrin transport / Transferrin endocytosis and recycling / positive regulation of isotype switching / Differentiation of keratinocytes in interfollicular epidermis in mammalian skin / response to copper ion / response to iron ion / RND1 GTPase cycle / response to manganese ion / RND2 GTPase cycle / positive regulation of bone resorption / RHOB GTPase cycle / Golgi Associated Vesicle Biogenesis / RHOC GTPase cycle / RHOJ GTPase cycle / RHOQ GTPase cycle / CDC42 GTPase cycle / RHOH GTPase cycle / RHOG GTPase cycle / transport across blood-brain barrier / RHOA GTPase cycle / RAC2 GTPase cycle / RAC3 GTPase cycle / response to nutrient / response to retinoic acid / positive regulation of T cell proliferation / clathrin-coated pit / positive regulation of B cell proliferation / Hsp70 protein binding / RAC1 GTPase cycle / osteoclast differentiation / clathrin-coated endocytic vesicle membrane / cellular response to leukemia inhibitory factor / acute-phase response / positive regulation of protein-containing complex assembly / HFE-transferrin receptor complex / recycling endosome / receptor internalization / positive regulation of protein localization to nucleus / cellular response to xenobiotic stimulus / recycling endosome membrane / Cargo recognition for clathrin-mediated endocytosis / positive regulation of peptidyl-serine phosphorylation / double-stranded RNA binding / extracellular vesicle / Clathrin-mediated endocytosis / virus receptor activity / melanosome / positive regulation of NF-kappaB transcription factor activity / positive regulation of canonical NF-kappaB signal transduction / iron ion transport / basolateral plasma membrane / cytoplasmic vesicle / intracellular iron ion homeostasis / blood microparticle / endosome / endosome membrane / early endosome / response to hypoxia / intracellular signal transduction / positive regulation of protein phosphorylation / external side of plasma membrane / intracellular membrane-bounded organelle / positive regulation of gene expression / negative regulation of apoptotic process / protein-containing complex binding / protein kinase binding / perinuclear region of cytoplasm / cell surface / protein homodimerization activity / RNA binding / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() unidentified (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.54 Å | ||||||
![]() | Bansia, H. / Wang, T. / Gutierrez, D. / des Georges, A. | ||||||
Funding support | ![]()
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![]() | ![]() 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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PDBx/mmCIF format | ![]() | 264.9 KB | Display | ![]() |
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PDB format | ![]() | 206 KB | Display | ![]() |
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-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 45 KB | Display | |
Data in CIF | ![]() | 64.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 14874MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Assembly
Deposited unit | ![]()
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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