Structural basis for CD96 immune receptor recognition of nectin-like protein-5, CD155
| Autor: | Gabrielle M. Watson, Zhihui Fu, Richard Berry, Jamie Rossjohn, Felix A. Deuss |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Immune receptor Immunoglobulin domain Crystallography X-Ray Biochemistry Protein Structure Secondary Cell Line Inorganic Chemistry 03 medical and health sciences Protein Domains TIGIT Antigens CD Structural Biology Nectin Sf9 Cells Animals Humans General Materials Science CD155 Physical and Theoretical Chemistry Structural motif Molecular Biology 030304 developmental biology 0303 health sciences Binding Sites biology Chemistry 030302 biochemistry & molecular biology Condensed Matter Physics Cell biology Molecular Docking Simulation HEK293 Cells Ectodomain biology.protein Receptors Virus Immunoglobulin superfamily Protein Binding |
| Zdroj: | Acta Crystallographica Section A Foundations and Advances. 75:e91-e91 |
| ISSN: | 2053-2733 |
| DOI: | 10.1107/s2053273319094658 |
| Popis: | Summary CD96, DNAM-1, and TIGIT constitute a group of immunoglobulin superfamily receptors that are key regulators of tumor immune surveillance. Within this axis, CD96 recognizes the adhesion molecule nectin-like protein-5 (necl-5), although the molecular basis underpinning this interaction remains unclear. We show that the first immunoglobulin domain (D1) of CD96 is sufficient to mediate a robust interaction with necl-5, but not the DNAM-1 and TIGIT ligand, nectin-2. The crystal structure of CD96-D1 bound to the necl-5 ectodomain revealed that CD96 recognized necl-5 D1 via a conserved “lock-and-key” interaction observed across TIGIT:necl complexes. Specific necl-5 recognition was underpinned by a novel structural motif within CD96, namely an “ancillary key”. Mutational analysis showed that this specific residue was critical for necl-5 binding, while simultaneously providing insights into the unique ligand specificity of CD96. |
| Databáze: | OpenAIRE |
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