All-Atom Simulations Reveal the Effect of Membrane Composition on the Signaling of the NKG2A/CD94/HLA-E Immune Receptor Complex.

Understanding how membrane composition influences the dynamics and function of transmembrane proteins is crucial for the comprehensive elucidation of cellular signaling mechanisms and the development of targeted therapeutics. In this study, we employed all-atom molecular dynamics simulations to investigate the impact of different membrane compositions on the conformational dynamics of the NKG2A/CD94/HLA-E immune receptor complex, a key negative regulator of natural killer cell cytotoxic activity. Our results reveal significant variations in the behavior of the immune complex structure across five different membrane compositions, which include POPC, POPA, DPPC, and DLPC phospholipids, and a mixed POPC/cholesterol system.

Computational study of the HLTF ATPase remodeling domain suggests its activity on dsDNA and implications in damage tolerance.

The Helicase-Like Transcription Factor (HLTF) is member of the SWI/SNF-family of ATP dependent chromatin remodellers known primarily for maintaining genome stability. Biochemical and cellular assays support its multiple roles in DNA Damage Tolerance. However, the lack of sufficient structural data limits the comprehension of the molecular basis of its modes of action.

All-Atom Simulations Reveal the Intricacies of Signal Transduction upon Binding of the HLA-E Ligand to the Transmembrane Inhibitory CD94/NKG2A Receptor.

Natural killer (NK) cells play an important role in the innate immune response against tumors and various pathogens such as viruses and bacteria. Their function is controlled by a wide array of activating and inhibitory receptors, which are expressed on their cell surface. Among them is a dimeric NKG2A/CD94 inhibitory transmembrane (TM) receptor which specifically binds to the non-classical MHC I molecule HLA-E, which is often overexpressed on the surface of senescent and tumor cells.