Computer-aided design of PVR mutants with enhanced binding affinity to TIGIT.

ABSTRACT:

Background

TIGIT, as a novel immune checkpoint molecule involved in T cell and NK cell anergy, could induce the immune tolerance and escape through binding with its ligand PVR. Blockade of TIGIT/PVR is considered as a promising strategy in cancer immunotherapy. However, to facilitate the design of inhibitors targeting TIGIT/PVR, the structural characteristics and binding mechanism still need to be further studied.

Methods

In this study, molecular dynamics (MD) simulations and in silico mutagenesis were used to analyze the interaction between TIGIT and its ligand PVR. Then, PVR mutants were designed and their activities were determined by using TIGIT overexpressed Jurkat cells.

Results

The results suggested that the loops of PVR (CC' loop, C'C″ loop, and FG loop) under

SUBMITTER: Zhou X 

PROVIDER: S-EPMC7869511 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature