Intracellular Trafficking of Guanylate-Binding Proteins Is Regulated by Heterodimerization in a Hierarchical Manner

Guanylate-binding proteins (GBPs) belong to the dynamin family of large GTPases and represent the major IFN-γ-induced proteins. Here we systematically investigated the mechanisms regulating the subcellular localization of GBPs. Three GBPs (GBP-1, GBP-2 and GBP-5) carry a C-terminal CaaX-prenylation signal, which is typical for small GTPases of the Ras family, and increases the membrane affinity of proteins. In this study, we demonstrated that GBP-1, GBP-2 and GBP-5 are prenylated in vivo and that prenylation is required for the membrane association of GBP-1, GBP-2 and GBP-5. Using co-immunoprecipitation, yeast-two-hybrid analysis and fluorescence complementation assays, we showed for the first time that GBPs are able to homodimerize in vivo and that the membrane association of GBPs is regulated by dimerization similarly to dynamin. Interestingly, GBPs could also heterodimerize. This resulted in hierarchical positioning effects on the intracellular localization of the proteins. Specifically, GBP-1 recruited GBP-5 and GBP-2 into its own cellular compartment and GBP-5 repositioned GBP-2. In addition, GBP-1, GBP-2 and GBP-5 were able to redirect non-prenylated GBPs to their compartment in a prenylation-dependent manner. Overall, these findings prove in vivo the ability of GBPs to dimerize, indicate that heterodimerization regulates sub-cellular localization of GBPs and underscore putative membrane-associated functions of this family of proteins

Antimicrobial and Virucidal Potential of Morpholinium-Based Ionic Liquids

Witnessed by the ongoing spread of antimicrobial resistant bacteria as well as the recent global pandemic of the SARS-CoV-2 virus, the development of new disinfection strategies is of great importance, and novel substance classes as effective antimicrobials and virucides are urgently needed. Ionic liquids (ILs), low-melting salts, have been already recognized as efficient antimicrobial agents with prospects for antiviral potential. In this study, we examined the antiviral activity of 12 morpholinium based herbicidal ionic liquids with a tripartite test system, including enzyme inhibition tests, virucidal activity determination against five model viruses and activity against five bacterial species. The antimicrobial and enzymatic tests confirmed that the inhibiting activity of ILs corresponds with the number of long alkyl side chains and that [Dec2Mor]+ based ILs are promising candidates as novel antimicrobials. The virucidal tests showed that ILs antiviral activity depends on the type and structure of the virus, revealing enveloped Phi6 phage as highly susceptible to the ILs action, while the non-enveloped phages PRD1 and MS2 proved completely resistant to ionic liquids. Furthermore, a comparison of results obtained for P100 and P001 phages demonstrated for the first time that the susceptibility of viruses to ionic liquids can be dependent on differences in the phage tail structure

Hybrid electrochemical and biological treatment of herbicidal ionic liquids comprising the MCPA anion

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PLFA pattern of untreated zebrafish embryos (control) and embryos treated with [C₈,C₈,C₁,C₁N][Br] (LC₁₀, LC₃₀, LC₅₀) at 72 hpf.

<p>hpf: hours post fertilization; y-axis is divided into two sections with different scales; *: P < 0.05; **: P < 0.01.</p

Mean values (±STD) for unsaturation index (UI) of the PLFA fraction in zebrafish embryos treated with 2,4-DCP and [C₆,C₆,C₁,C₁N][Br] for LC₅₀ at 0.5, 24, 48 and 72 hpf.

<p>hpf: hours post fertilization; *: P < 0.05; **: P < 0.01.</p