Cureus, Journal Year: 2025, Volume and Issue: unknown
Published: April 14, 2025
COPA syndrome is a rare autoinflammatory disorder caused by mutations in the gene, leading to immune dysregulation and inflammatory pathology. The HAQ variant of stimulator interferon genes (STING) allele has been identified as protective factor against disease manifestation. Understanding molecular interaction between HAQ-STING critical for uncovering potential therapeutic strategies. This study utilized AlphaFold2 Multimer (AF2M) (DeepMind, London, UK) an extension designed predict structures protein complexes (multimers), analyze structural COPA, STING, HAQ-STING. PyMOL (Schrödinger, Inc., New York, USA) was used visualization analysis conformational differences protein-protein interactions (PPIs). Structural alignment binding pocket were conducted assess impact on function. Molecular docking studies with AutoDock Vina Extended (OneAngstrom, Grenoble, France). AF2M revealed that causes 90-degree rotational shift its orientation compared inducing significant rearrangements. alters COPA's stability, suggesting allosteric regulatory mechanism. A channel small molecule at interface STING COPA. If meets criteria depth, functional significance, it could be drug-binding pocket. docked two interacting proteins can disrupt complex. approach, known PPI inhibition, well-established strategy drug discovery. Fosfomycin, phosphate-containing molecule, STING. provides novel insights into role syndrome. induced may modulate signaling, preventing COPA; fosfomycin this channel. These findings highlight avenues, including gene therapy, small-molecule inhibitors, pathway modulation. Further experimental validation needed translate these clinical applications.
Language: Английский