Identification of small-molecule protein-protein interaction inhibitors for NKG2D.

ABSTRACT: NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ⁺, and CD8⁺ T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein-protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2

SUBMITTER: Thompson AA 

PROVIDER: S-EPMC10160951 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature