ArticleThe EMBO journal2022
NKG2D discriminates diverse ligands through selectively mechano-regulated ligand conformational changes.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 56 citations in OpenAlex.
- Harnessing the NKG2D immune surveillance pathway using engineered T-cells for the treatment of human disease.Human vaccines & immunotherapeutics · 2026Review
- Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces.Science advances · 2026Article
- Stem cell-directed targeted chemotherapy primes drug-resistant metastatic ovarian tumors for elimination by natural killer cells.Molecular therapy. Oncology · 2026Article
- [Research progress of the ULBP-NKG2D axis in autoimmune diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- The dual roles of natural killer cells in liver immunity and tolerance: Implications for health and disease.Hepatology communications · 2026Review
- Neoadjuvant mFOLFOX6 plus camrelizumab and apatinib in colon cancer and biomarker research via spatiotemporal-omics profiling.NPJ precision oncology · 2026Article
- Mechanical force regulates the inhibitory function of PD-1.EMBO reports · 2026Article
- Injectable microgels carrying engineered biomimetic nanoparticles for osteoarthritis therapy via dual-targeted senescent chondrocyte clearance and endogenous repair promotion.Bioactive materials · 2026Article
- Engineering NKG2D ligand affinity transforms EGFR-targeted NK cell engagers into high-potency effectors against pancreatic cancer.Journal of biological engineering · 2026Article
- Mechanical communication and function regulation of immune cells.Fundamental research · 2026Review
- Resting-state spatial statistics of NK cell receptors may improve early signal discrimination.Biophysical journal · 2026Article
- Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces.bioRxiv : the preprint server for biology · 2026Article
- Update on the role of mycobiome in Gastrointestinal cancers: mechanisms and therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025Review
- MicroRNA-122 regulates inflammatory and autophagic proteins by downregulating pyruvate kinase M2 in non-alcoholic fatty liver disease.Molecular and cellular biochemistry · 2025Article
- Two major human phenotypes of MICA molecules and their differential activation to NK cells via NKG2D receptor.Frontiers in immunology · 2025Article
- Tandem CAR T-cells targeting CD19 and NKG2DL can overcome CD19 antigen escape in B-ALL.Frontiers in immunology · 2025Article
- Genes and Pathways Underpinning Klinefelter Syndrome at Bulk and Single-Cell Levels.Biochemical genetics · 2024Article
- Mechanotransduction governs CD40 function and underlies X-linked hyper-IgM syndrome.Science advances · 2024Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulatory immune receptor NKG2D binds diverse ligands to elicit differential anti-tumor and anti-virus immune responses. Two conflicting degeneracy recognition models based on static crystal structures and in-solution binding affinities have been considered for almost two decades. Whether and how NKG2D recognizes and discriminates diverse ligands still remain unclear. Using live-cell-based single-molecule biomechanical assay, we characterized the in situ binding kinetics of NKG2D interacting with different ligands in the absence or presence of mechanical force. We found that mechanical force application selectively prolonged NKG2D interaction lifetimes with the ligands MICA and MICB, but not with ULBPs, and that force-strengthened binding is much more pronounced for MICA than for other ligands. We also integrated steered molecular dynamics simulations and mutagenesis to reveal force-induced rotational conformational changes of MICA, involving formation of additional hydrogen bonds on its binding interface with NKG2D, impeding MICA dissociation under force. We further provided a kinetic triggering model to reveal that force-dependent affinity determines NKG2D ligand discrimination and its downstream NK cell activation. Together, our results demonstrate that NKG2D has a discrimination power to recognize different ligands, which depends on selective mechanical force-induced ligand conformational changes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.