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
AbstractCD160 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.
|Journal series||Oncotarget, ISSN 1949-2553, (A 35 pkt)|
|Publication size in sheets||0.7|
|Keywords in English||CD160, HVEM, immune checkpoints, hydrogen/deuterium exchange combined to mass spectrometry, molecular modeling|
|License||Journal (articles only); published final; ; with publication|
|Score||= 35.0, 24-07-2019, ArticleFromJournal|
|Publication indicators||: 2017 = 1.039; : 2016 = 5.168 (2) - 2016=5.312 (5)|
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