1. Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81.
- Author
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Susa KJ, Rawson S, Kruse AC, and Blacklow SC
- Subjects
- Amino Acid Sequence, Antibodies, Monoclonal, Humanized chemistry, Antibodies, Monoclonal, Humanized immunology, Antigens, CD19 immunology, B-Lymphocytes immunology, Cryoelectron Microscopy, Humans, Maytansine analogs & derivatives, Maytansine chemistry, Maytansine immunology, Models, Molecular, Mutation, Protein Binding, Protein Domains, Receptors, Antigen, B-Cell immunology, Tetraspanin 28 genetics, Tetraspanin 28 immunology, Antigens, CD19 chemistry, Receptors, Antigen, B-Cell chemistry, Tetraspanin 28 chemistry
- Abstract
Signaling through the CD19-CD81 co-receptor complex, in combination with the B cell receptor, is a critical determinant of B cell development and activation. It is unknown how CD81 engages CD19 to enable co-receptor function. Here, we report a 3.8-angstrom structure of the CD19-CD81 complex bound to a therapeutic antigen-binding fragment, determined by cryo-electron microscopy (cryo-EM). The structure includes both the extracellular domains and the transmembrane helices of the complex, revealing a contact interface between the ectodomains that drives complex formation. Upon binding to CD19, CD81 opens its ectodomain to expose a hydrophobic CD19-binding surface and reorganizes its transmembrane helices to occlude a cholesterol binding pocket present in the apoprotein. Our data reveal the structural basis for CD19-CD81 complex assembly, providing a foundation for rational design of therapies for B cell dysfunction., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2021
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