A structural model of the immune checkpoint CD160-HVEM complex derived from HDX-mass spectrometry and molecular modeling

Katarzyna Kuncewicz , Marta Spodzieja , Adam Sieradzan , Agnieszka Karczyńska , Katarzyna Dąbrowska , Michał Dadlez , Daniel E. Speiser , Laurent Derre , Sylwia Rodziewicz-Motowidło

Abstract

CD160 is a T cell coinhibitory molecule that interacts with the herpes virus entry mediator (HVEM) on antigen-presenting cells to provide an inhibitory signal to T cells. To date, the structure of CD160 and its complex with HVEM are unknown. Here, we have identified the fragments of CD160 interacting with HVEM using ELISA tests, hydrogen/deuterium studies, affinity chromatography and mass spectrometry (MS). By combining hydrogen/deuterium exchange and mass spectrometry (HDX-MS) we obtained key information about the tertiary structure of CD160, predicting the 3D structure of the CD160–HVEM complex. Our results provide insights into the molecular architecture of this complex, serving as a useful basis for designing inhibitors for future immunotherapies.
Author Katarzyna Kuncewicz (FCh / DBCh / LMCh)
Katarzyna Kuncewicz,,
- Laboratory of Medical Chemistry
, Marta Spodzieja (FCh / DBCh / LMCh)
Marta Spodzieja,,
- Laboratory of Medical Chemistry
, Adam Sieradzan (FCh / DTCh / LMM)
Adam Sieradzan,,
- Laboratory of Molecular Modeling
, Agnieszka Karczyńska (FCh / DTCh / LMM)
Agnieszka Karczyńska,,
- Laboratory of Molecular Modeling
, Katarzyna Dąbrowska
Katarzyna Dąbrowska,,
-
, Michał Dadlez
Michał Dadlez,,
-
, Daniel E. Speiser
Daniel E. Speiser,,
-
, Laurent Derre
Laurent Derre,,
-
, Sylwia Rodziewicz-Motowidło (FCh / DBCh / LMCh)
Sylwia Rodziewicz-Motowidło,,
- Laboratory of Medical Chemistry
Journal seriesOncotarget, ISSN 1949-2553, (A 35 pkt)
Issue year2019
Vol10
No4
Pages536-550
Publication size in sheets0.7
Keywords in EnglishCD160, HVEM, immune checkpoints, hydrogen/deuterium exchange combined to mass spectrometry, molecular modeling
ASJC Classification2730 Oncology
DOIDOI:10.18632/oncotarget.26570
URL https://doi.org/10.18632/oncotarget.26570
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)35
ScoreMinisterial score = 35.0, 24-07-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.039; WoS Impact Factor: 2016 = 5.168 (2) - 2016=5.312 (5)
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