Abstract - Bundschuh
Unraveling the interplay between the dynamics, polymerization and membrane binding of guanylate binding proteins and implications on membrane stability
Guanylate binding proteins (GBPs) are a family of large interferon-inducible GTPases and dynamin-like proteins (DLPs) that play a crucial role in defending against viral and bacterial infections. In both humans and mice, certain GBPs are essential for immunity against intracellular pathogens, including Shigella Flexneri and Toxoplasma gondii [1-2]. Our research focuses on hGBP1, mGBP2, and mGBP7, which target and disrupt parasitophorous vacuolar membranes in mice and bacterial-associated lipopolysaccharide (LPS) membranes in humans. While ongoing biochemical studies aim to characterize these GBPs, the molecular mechanisms underlying their protective functions remain unclear. To bridge this knowledge gap, we employ multiscale molecular dynamics (MD) simulations—both all-atom (AA) and coarse-grained (CG)—to investigate how large-scale conformational changes, protein multimerization, and membrane interactions contribute to their function.
Bastian Bundschuh, Wibke Schumann, Jennifer Loschwitz, Birgit Strodel - Heinrich-Heine-Universität Düsseldorf