Abstract
CD160 is a signaling molecule that interacts with herpes virus entry mediator (HVEM) and contributes to a wide range of immune responses, including T cell inhibition, natural killer cell activation, and mucosal immunity. GPI-anchored and transmembrane isoforms of CD160 share the same ectodomain responsible for HVEM engagement, which leads to bidirectional signaling. Despite the importance of the CD160:HVEM signaling axis and its therapeutic relevance, the structural and mechanistic basis underlying CD160-HVEM engagement has not been described. We report the crystal structures of the human CD160 extracellular domain and its complex with human HVEM. CD160 adopts a unique variation of the immunoglobulin fold and exists as a monomer in solution. The CD160:HVEM assembly exhibits a 1:1 stoichiometry and a binding interface similar to that observed in the BTLA:HVEM complex. Our work reveals the chemical and physical determinants underlying CD160:HVEM recognition and initiation of associated signaling processes. Liu et al. determined the structures of human CD160 and its complex with HVEM, revealing the atomic basis for CD160:HVEM recognition. These structures highlight an intermolecular antiparallel β-sheet organization that supports the promiscuous binding properties of HVEM, enabling recognition of CD160, BTLA, and herpes simplex virus glycoprotein D.
Original language | English (US) |
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Pages (from-to) | 1286-1295.e4 |
Journal | Structure |
Volume | 27 |
Issue number | 8 |
DOIs | |
State | Published - Aug 6 2019 |
Keywords
- CD160 and HVEM
- IgSF and TNFRSF interactions
- Interaction promiscuity
- T cell costimulation and coinhibition
- X-ray structures
- immune regulation
- intermolecular beta-sheet
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology