Oncotarget

Research Papers:

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 _

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

Oncotarget. 2019; 10:536-550. https://doi.org/10.18632/oncotarget.26570

Metrics: PDF 126 views  |   HTML 175 views  |   ?  


Abstract

Katarzyna Kuncewicz1, Marta Spodzieja1, Adam Sieradzan2, Agnieszka Karczyńska2, Katarzyna Dąbrowska3, Michał Dadlez3, Daniel E. Speiser4, Laurent Derre5 and Sylwia Rodziewicz-Motowidło1

1University of Gdansk, Faculty of Chemistry, Department of Biomedical Chemistry, Gdansk, Poland

2University of Gdansk, Faculty of Chemistry, Department of Theoretical Chemistry, Gdansk, Poland

3Polish Academy of Sciences, Institute of Biochemistry and Biophysics, Mass Spectrometry Laboratory, Warsaw, Poland

4Ludwig Cancer Research Center, Department of Oncology, Epalinges, Switzerland

5University Hospital of Lausanne (CHUV), Urology Department, Urology Research Unit, Lausanne, Switzerland

Correspondence to:

Sylwia Rodziewicz-Motowidło, email: s.rodziewicz-motowidlo@ug.edu.pl

Keywords: CD160; HVEM; immune checkpoints; hydrogen/deuterium exchange combined to mass spectrometry; molecular modeling

Received: May 13, 2018     Accepted: December 10, 2018     Published: January 11, 2019

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 26570