Macrophage reprogramming by negatively-charged membrane phospholipids controls infection
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ABSTRACT:
PROVIDER: PRJNA475156 | ENA |
REPOSITORIES: ENA
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Project description:<p>Tick-borne encephalitis virus is an enveloped, pathogenic, RNA virus in the family Flaviviridae, genus Flavivirus. Viral particles are formed when the nucleocapsid, consisting of an RNA genome and multiple copies of the capsid protein, buds through the endoplasmic reticulum membrane and acquires the viral envelope and the associated proteins. The coordination of the nucleocapsid components to the sites of assembly and budding are poorly understood. Here, we investigate nucleocapsid assembly by characterizing the interactions of the wild-type and truncated capsid proteins with membranes by using biophysical methods and model membrane systems. We show that capsid protein initially binds membranes via electrostatic interactions with negatively-charged lipids which is followed by membrane insertion. Additionally, we show that membrane-bound capsid protein can recruit viral genomic RNA. We confirm the biological relevance of the biophysical findings by using mass spectrometry to show that purified virions contain negatively-charged lipids. Our results suggest that nucleocapsid assembly is coordinated by negatively-charged membrane patches on the endoplasmic reticulum and that the capsid protein mediates direct contacts between the nucleocapsid and the membrane.</p>
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Project description:The endoplasmic reticulum (ER) supports biosynthesis of proteins with diverse transmembrane domain (TMD) lengths and hydrophobicity. Features in transmembrane domains such as charged residues in ion channels are often functionally important, but could pose a challenge during cotranslational membrane insertion and folding. Our systematic proteomic approaches in both yeast and human cells revealed that the ER membrane protein complex (EMC) binds to and promotes the biogenesis of a range of multipass transmembrane proteins, with a particular enrichment for transporters. Proximity-specific ribosome profiling demonstrates that the EMC engages clients cotranslationally and immediately following clusters of TMDs enriched for charged residues. The EMC can remain associated after completion of translation, which both protects clients from premature proteasomal degradation and allows recruitment of substrate-specific and general chaperones. Thus, the EMC broadly enables the biogenesis of multipass transmembrane proteins containing destabilizing features, thereby mitigating the trade-off between function and stability.
2018-05-29 | GSE112891 | GEO
Project description:Plasma membrane repair is a rapid cellular response for resealing of membrane for cell survival. In the early step of repair process, TRIM72 is known to a key initiator for facilitating patch membrane to the damaged membrane site. When acute membrane injury happens, TRIM72 is also known to sensitively generate disulfide bonds formations by reactive oxygen species and further oligomerize with each other. We tried to clarify this repair system using in vitro reconstruction of TRIM72-liposome complex and find critical sites using cross-linker mass spectrometry. Using each four different length of sulfhydryl reactive cross-linkers, TRIM72 cross-linked with each other on the negatively charged liposome surface only. We also identified that the cross-linking bridges were highly conserved except bismaleimidoethane as a shortest arm length about 8 Å only. Our results indicated that the B2-box/B2-box locates closely with each other on the liposome surface. Furthermore, freely open RING domain is rearranged into the specific conformation, where located near the H2 helix of coiled coil domain. It suggests that the conformational changes of TRIM72 are induced by higher order assembly on the negative charged membrane surface.
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Project description:Primary objectives: Characterization of the macrophage population subset that is modulated by enteric neurons
Primary endpoints: Characterization of the macrophage population subset that is modulated by enteric neurons via RNA sequencing
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Project description:This study investigates the effects of cyclodipeptide on fungal and nematode metabolism, specifically focusing on its impact on membrane composition and metabolic responses. Metabolomic profiles of treated and untreated fungal cultures were compared to unravel the molecular changes induced by cyclodipeptide, with a particular emphasis on membrane phospholipids such as monoolein and phosphatidyl ethanolamine, as well as other plasma membrane components like ergosterol and its derivative products. The results reveal significant alterations in the metabolites present in the presence of cyclodipeptide. Specifically, the levels of cyclo (Pro-Tyr) monoolein were found to decrease, while phosphatidyl ethanolamine levels increased. Moreover, the levels of ergosterol and its derivatives were observed to decrease as well. These findings indicate that cyclodipeptide has a profound impact on the metabolic pathways of the fungal system under investigation. The study suggests that cyclodipeptide not only influences membrane phospholipids but may also have broader effects on membrane proteins, cellular signaling, and communication. Furthermore, the observed changes in metabolomic profiles hint at potential alterations in cellular processes beyond membrane composition, possibly involving gene expression and enzyme activity. Understanding the mechanisms behind these effects holds considerable scientific interest and practical implications. The ability of cyclodipeptide to selectively target membrane components presents opportunities for studying and manipulating membrane function in various organisms. Additionally, the discovery of new bioactive natural products like cyclodipeptide opens avenues for developing innovative therapeutics or agricultural agents. Further research is needed to fully comprehend the intricate mechanisms underlying the observed effects of cyclodipeptide on fungal metabolism.
2023-07-23 | GSE237225 | GEO
Project description:This study investigates the effects of cyclodipeptide on fungal and nematode metabolism, specifically focusing on its impact on membrane composition and metabolic responses. Metabolomic profiles of treated and untreated fungal cultures were compared to unravel the molecular changes induced by cyclodipeptide, with a particular emphasis on membrane phospholipids such as monoolein and phosphatidyl ethanolamine, as well as other plasma membrane components like ergosterol and its derivative products. The results reveal significant alterations in the metabolites present in the presence of cyclodipeptide. Specifically, the levels of cyclo (Pro-Tyr) monoolein were found to decrease, while phosphatidyl ethanolamine levels increased. Moreover, the levels of ergosterol and its derivatives were observed to decrease as well. These findings indicate that cyclodipeptide has a profound impact on the metabolic pathways of the fungal system under investigation. The study suggests that cyclodipeptide not only influences membrane phospholipids but may also have broader effects on membrane proteins, cellular signaling, and communication. Furthermore, the observed changes in metabolomic profiles hint at potential alterations in cellular processes beyond membrane composition, possibly involving gene expression and enzyme activity. Understanding the mechanisms behind these effects holds considerable scientific interest and practical implications. The ability of cyclodipeptide to selectively target membrane components presents opportunities for studying and manipulating membrane function in various organisms. Additionally, the discovery of new bioactive natural products like cyclodipeptide opens avenues for developing innovative therapeutics or agricultural agents. Further research is needed to fully comprehend the intricate mechanisms underlying the observed effects of cyclodipeptide on fungal metabolism.
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