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Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81.

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.

SUBMITTER: Susa KJ

PROVIDER: S-EPMC8111558 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81.

Susa Katherine J KJ Rawson Shaun S Kruse Andrew C AC Blacklow Stephen C SC

Science (New York, N.Y.) 20210101 6526

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 ...[more]

PMID: 33446559

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