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, (N/A 100 pkt)|
|Publication size in sheets||0.70|
|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||= 100.0, 26-06-2020, ArticleFromJournal|
|Publication indicators||= 1.000; : 2018 = 0.904; : 2016 = 5.168 (2) - 2016=5.312 (5)|
|Citation count*||2 (2020-06-25)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.