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 - [Institute of Biochemistry and Biophysics of the Polish Academy of Sciences]
Katarzyna Dąbrowska,,
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- Institute of Biochemistry and Biophysics of the Polish Academy of Sciences
, Michał Dadlez - [Institute of Biochemistry and Biophysics of the Polish Academy of Sciences]
Michał Dadlez,,
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- Institute of Biochemistry and Biophysics of the Polish Academy of Sciences
, Daniel E. Speiser - [Ludwig Institute for Cancer Research Lausanne]
Daniel E. Speiser,,
-
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, Laurent Derre - [Centre Hospitalier Universitaire Vaudois]
Laurent Derre,,
-
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, Sylwia Rodziewicz-Motowidło (FCh/DBCh/LMCh)
Sylwia Rodziewicz-Motowidło,,
- Laboratory of Medical Chemistry
Journal seriesOncotarget, ISSN 1949-2553, (N/A 100 pkt)
Issue year2019
Vol10
No4
Pages536-550
Publication size in sheets0.70
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)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 26-06-2020, ArticleFromJournal
Publication indicators Scopus Citations = 1.000; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.904; WoS Impact Factor: 2016 = 5.168 (2) - 2016=5.312 (5)
Citation count*2 (2020-06-25)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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