دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81.
المؤلفون: Susa KJ; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA., Rawson S; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA., Kruse AC; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. stephen_blacklow@hms.harvard.edu andrew_kruse@hms.harvard.edu., Blacklow SC; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. stephen_blacklow@hms.harvard.edu andrew_kruse@hms.harvard.edu.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
المصدر: Science (New York, N.Y.) [Science] 2021 Jan 15; Vol. 371 (6526), pp. 300-305.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
أسماء مطبوعة: Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
مواضيع طبية MeSH: Antigens, CD19/*chemistry , Receptors, Antigen, B-Cell/*chemistry , Tetraspanin 28/*chemistry, 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
مستخلص: 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.)
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معلومات مُعتمدة: DP5 OD021345 United States OD NIH HHS; F31 HL147459 United States HL NHLBI NIH HHS; R35 CA220340 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Antibodies, Monoclonal, Humanized)
0 (Antigens, CD19)
0 (Receptors, Antigen, B-Cell)
0 (Tetraspanin 28)
14083FR882 (Maytansine)
MRS84YT9L2 (coltuximab ravtansine)
تواريخ الأحداث: Date Created: 20210115 Date Completed: 20210210 Latest Revision: 20210521
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8111558
DOI: 10.1126/science.abd9836
PMID: 33446559
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-9203
DOI:10.1126/science.abd9836