Structural Basis of CD160:HVEM Recognition

Weifeng Liu, Sarah C. Garrett, Elena V. Fedorov, Udupi A. Ramagopal, Scott J. Garforth, Jeffrey B. Bonanno, Steven C. Almo

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1286-1295.e4
JournalStructure
Volume27
Issue number8
DOIs
StatePublished - Aug 6 2019

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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

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