Authors: Martha Powell, Future Science Group
New research has gained insights into an immune defense strategy by which pathogens are engulfed in membrane vesicles. The study has identified the mechanisms of human guanylate-binding protein 1 (hGBP1), giving a better understanding of this critical pathogen-response process.
It has previously been reported that guanylate-binding proteins are involved in antimicrobial activities; however, the mechanisms behind this have been poorly understood. In this study, published recently in the Proceedings of the National Academy of Sciences, the team utilized a combination of biochemical and cell biology experiments to investigate the function of hGBP1.
The researchers discovered that when GTP, an energy storage molecule, was bound to hGBP1 this triggered a structural change in the protein, releasing a lipid anchor. The team went on to demonstrate that this anchor allowed polymerization of hGBP1, enabling it to form large ring-shaped polymers.
In addition, the team discovered that the GTP interaction also allowed hGBP1 to attach to lipid membranes. Using artificial vesicles as a lipid bilayer model the team demonstrated that hGBP1 employs its lipid anchor to bind vesicle membranes.
This GTP-dependent membrane binding could be a precursor to vesicle fusion and therefore could play a role in the clearance of pathogens. Vesicle fusion is crucial to immune defense mechanisms, as pathogens are engulfed into vesicles that subsequently merge with organelles and lysosomes to enable degradation.
These findings report a nucleotide-controlled function of hGBP1, giving deeper insights into this protein’s molecular mechanism in the course of pathogen response.
Sources: Shydlovskyi S, Zienert AY, Ince S et al. Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1. Proc. Natl Acad. Sci. doi:10.1073/pnas.1620959114 (2017) (Epub ahead of print); http://news.rub.de/english/press-releases/2017-07-03-immune-defence-mechanism-how-proteins-bring-together-membrane-blebs