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Updated: Jan 17, 2026
Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
Published on: September 28, 2018
Structural insights into the impacts of non-synonymous single nucleotide polymorphisms in CD274 gene on the
Syed Sahajada Mahafujul Alam1, Arijit Samanta1, Safdar Ali2
1Applied Biochemistry Laboratory, Department of Biological Sciences, Aliah University, Kolkata, 700160, India.
Abstract:
Programmed cell death ligand 1 (PD-L1) on tumor cells interacts with PD-1 of activated T cells causing immune evasion. Polymorphisms in CD274 gene encoding PD-L1 have been associated with several cancer types. In this study, various bioinformatics tools were employed to identify the most deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in CD274 gene that could alter the structure and function of PD-L1. A database search through cBioPortal, ClinVar, COSMIC, gnomAD and HGMD identified total 137 nsSNPS located at the IgV domain of PD-L1 responsible for receptor binding. These mutations were further screened by several insilico tools: PolyPhen2, PhD-SNP, FATHMM, Meta-SNP, PANTHER-PSEP, SIFT, MutPred2, mCSM, MUpro, I-mutant 2.0, INPS-MD, ConSurf, HOPE, and NetSurfP-3.0 for determining the impact of these mutations on the structure of PD-L1. Based on the consensus among various algorithms, 39 nsSNPs were identified to have deleterious effects, including altered protein stability. The binding affinity of mutated PD-L1 proteins with PD-1 was studied by molecular docking and dynamic simulations. Two highly conserved nsSNPs, C40R and V104L were found to enhance binding affinity to PD-1, with a greater impact on structure and function. These results underline the potential structural and functional consequences of these nsSNPs on PD-L1.
Insights
Genetic variations in the CD274 gene, encoding programmed cell death ligand 1 (PD-L1), can impact cancer immunity. This study identified specific PD-L1 nsSNPs that may alter its structure and enhance binding to PD-1, affecting immune evasion.
Area of Science:
- Genomics
- Immunology
- Bioinformatics
Background:
- Programmed cell death ligand 1 (PD-L1) on tumor cells interacts with PD-1 on T cells, mediating immune evasion in cancer.
- Genetic variations (polymorphisms) in the CD274 gene, which encodes PD-L1, are linked to various cancer types.
Purpose of the Study:
- To identify deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in the CD274 gene using bioinformatics tools.
- To assess the impact of these nsSNPs on PD-L1 structure, function, and binding affinity to PD-1.
Main Methods:
- Utilized databases (cBioPortal, ClinVar, COSMIC, gnomAD, HGMD) to identify nsSNPs in the PD-L1 IgV domain.
- Employed multiple in silico tools (PolyPhen2, SIFT, MutPred2, etc.) to predict the functional impact of nsSNPs.
- Performed molecular docking and dynamic simulations to evaluate the binding affinity of mutated PD-L1 to PD-1.
Main Results:
- Identified 137 nsSNPs in the PD-L1 IgV domain; 39 were predicted to have deleterious effects, including altered protein stability.
- Two highly conserved nsSNPs, C40R and V104L, were found to enhance the binding affinity of PD-L1 to PD-1.
- These nsSNPs significantly impact PD-L1 structure and function, potentially influencing immune evasion.
Conclusions:
- Specific nsSNPs in the CD274 gene can structurally and functionally alter PD-L1.
- The identified nsSNPs, particularly C40R and V104L, may enhance PD-L1/PD-1 interactions, contributing to cancer immune evasion.
- These findings highlight the clinical relevance of CD274 gene polymorphisms in cancer immunotherapy.
