Structural requirements for membrane binding of human guanylate?binding protein 1

Human guanylate-binding protein 1 (hGBP1) is a key player in innate immunity and fights diverse intracellular microbial pathogens. Its antimicrobial functions depend on hGBP1’s GTP binding- hydrolysis-induced abilities to form large, structured polymers attach lipid membranes. Crucial for both of these biochemical features the nucleotide-controlled release C terminally located farnesyl moiety. Here, we address molecular details hGBP1 membrane binding mechanism by employing recombinant, fluorescently labeled hGBP1, artificial We demonstrate importance GTPase activity resulting structural rearrangement molecule, which term open state. This state supported stabilized homodimer contacts involving middle domain further bilayer surface. show that surface monolayer built pins pincushion-like arrangement with tail integrated N-terminal facing outwards. suggest similar intramolecular between neighboring molecules are responsible polymer formation Finally, tethering large unilamellar vesicles occurs after vesicle fully covered monolayer. Both hGBP1-induced have implications understanding combating bacterial Databases Structural data available RCSB Protein Data Bank under accession numbers: 6K1Z, 2D4H.