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A07: Unravelling the interactions of mGBP proteins with lipid membranes

Dynamin-related guanylate binding proteins (GBPs) are a family of large interferon-inducible GTPases and dynamin-like proteins involved in host defense against viral and bacterial pathogens. Certain human and mouse GBPs (hGBPs and mGBPs) are essential for immunity against intracellular pathogens, including Toxoplasma gondii. The focus of this project is on hGBP1, mGBP2, and mGBP7, which have been shown to bind and damage parasite-associated membranes, including the parasitophorous vacuolar membrane (PVM) of T. gondii in the case of mGBP2 and mGBP7. Biochemical and biophysical characterization of these GBPs is being pursued in projects A06, A01/CSS, Z01 and Z02; however, many questions remain about the molecular mechanisms of protection by these GBPs. To address this knowledge gap, we harness the power of multiscale molecular dynamics (MD) simulations at the all-atom and coarse-grained (CG) level, to unravel the interplay between large-scale conformational transitions, protein multimerization, and binding to pathogenic membranes.Dynamin-related guanylate binding proteins (GBPs) are a family of large interferon-inducible GTPases and dynamin-like proteins involved in host defense against viral and bacterial pathogens. Certain human and mouse GBPs (hGBPs and mGBPs) are essential for immunity against intracellular pathogens, including Toxoplasma gondii. The focus of this project is on hGBP1, mGBP2, and mGBP7, which have been shown to bind and damage parasite-associated membranes, including the parasitophorous vacuolar membrane (PVM) of T. gondii in the case of mGBP2 and mGBP7. Biochemical and biophysical characterization of these GBPs is being pursued in projects A06, A01/CSS, Z01 and Z02; however, many questions remain about the molecular mechanisms of protection by these GBPs. To address this knowledge gap, we harness the power of multiscale molecular dynamics (MD) simulations at the all-atom and coarse-grained (CG) level, to unravel the interplay between large-scale conformational transitions, protein multimerization, and binding to pathogenic membranes.

Project leader: Prof. Dr. Birgit Strodel, ,                    

Researchers: Jennifer Loschwitz,  
                           Dr. Hebah Fatafta,
                          
 

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