Glue it together: self-assembly of the antibacterial GTPase GBP1

Guanylate-binding proteins (GBPs) are interferon-inducible large GTPases that play a central role in cell-autonomous immunity against intracellular bacterial pathogens. A defining feature of GBPs is their ability to translate GTP binding and hydrolysis into large-scale conformational rearrangements that drive self-assembly into higher-order structures, including dimers, polymers, and membrane-associated coatomers. This review integrates insights from biochemical, biophysical, structural, and cell biology studies to summarize current mechanistic models of GBP self-assembly, with a particular focus on human GBP1. We highlight how GTP hydrolysis-driven GBP1 polymers and coatomers act as self-regulating nanomachineries that recognize and remodel the pathogen-associated molecular pattern lipopolysaccharide, thereby fulfilling a dual function as immune sensor and effector in non-canonical inflammasome activation and bacterial membrane disruption. By directly linking nucleotide binding kinetics, enzymatic activity, and assembly dynamics to cellular and infection-related phenotypes, this review places decades of biochemical and biophysical work on GBP1 into a clear physiological context of antibacterial host defense.