Structural Basis of CD160:HVEM Recognition

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

doi:10.1016/j.str.2019.05.010

Title: Structural Basis of CD160:HVEM Recognition

Journal Article · Thu Aug 01 00:00:00 EDT 2019 · Structure

DOI:https://doi.org/10.1016/j.str.2019.05.010· OSTI ID:1646509

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

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. Finally, our work reveals the chemical and physical determinants underlying CD160:HVEM recognition and initiation of associated signaling processes.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIG)

Grant/Contract Number:: AC02-98CH10886; AC02-06CH11357; S10 OD020068

OSTI ID:: 1646509

Alternate ID(s):: OSTI ID: 1562695

Journal Information:: Structure, Journal Name: Structure Vol. 27 Journal Issue: 8; ISSN 0969-2126

Publisher:: ElsevierCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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Cited by: 23 works

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59 BASIC BIOLOGICAL SCIENCES
CD160 and HVEM
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Title: Structural Basis of CD160:HVEM Recognition

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