The unique cell envelope structure of Mycobacterium tuberculosis is fundamental to its pathogenesis. Phosphatidylinositol (PI)-anchored glycolipids, such as phosphatidylinositol mannosides (PIMs), lipomannan and lipoarabinomannan, are essential components of the cell envelope widely conserved among mycobacteria, but their roles in the cell envelope integrity are not fully understood. We previously identified PimE in Mycobacterium smegmatis, a nonpathogenic model organism, as a mannosyltransferase that catalyzes the fifth mannose transfer for the biosynthesis of hexamannosyl PIMs. Our analyses, reported here, further demonstrate that the growth of the pimE deletion mutant (ΔpimE) is defective in the presence of copper. We first found that the small colony phenotype of ΔpimE on a solid Middlebrook 7H10 agar surface was alleviated when grown on M63 agar. Comparative analysis of the two media led us to identify copper in Middlebrook 7H10 as the cause of growth retardation seen in ΔpimE. We further demonstrated that ΔpimE is sensitized to several antibiotics, but the increased sensitivities were independent of the presence of copper. We conclude that the deletion of the pimE gene does not cause growth defects under optimal growth conditions, but makes the cell envelope vulnerable to toxic compounds such as copper and antibiotics.
The microtubule motor cytoplasmic dynein-1 transports and positions various organelles, but the molecular basis of this functional diversity is not fully understood. Cargo adaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi and human cells by forming the FTS-Hook-FHIP (FHF) complex. By contrast, the Hook homolog ZYG-12 recruits dynein to the nuclear envelope (NE) in the meiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex.
Calcium (Ca)-activated ion channels and lipid scramblases in the transmembrane protein 16 (TMEM16) family are structurally related to mechanosensitive ion channels in the TMEM63 and transmembrane channel-like (TMC) families. Members of this structurally related superfamily share similarities in gating transitions and serve a wide range of physiological functions, which is evident from their disease associations. The TMEM16, TMEM63 and TMC families include members with important functions in the cell membrane and/or intracellular organelles such as the endoplasmic reticulum, membrane contact sites, endosomes and lysosomes.
Unlabelled: Bacteria have evolved diverse strategies to ensure survival under nutrient-limited conditions, where rapid energy generation is not achievable. Here, we performed a transposon insertion site sequencing loss-of-function screen to identify genes that promote pathogen fitness in stationary phase. We discovered that the aintenance of ipid symmetry (Mla) pathway, which is crucial for transferring phospholipids from the outer to the inner membrane, is critical for stationary phase fitness.
Human RAD52 is a prime target for synthetical lethality approaches to treat cancers with deficiency in homologous recombination. Among multiple cellular roles of RAD52, its functions in homologous recombination repair and protection of stalled replication forks appear to substitute those of the tumor suppressor protein BRCA2. However, the mechanistic details of how RAD52 can substitute BRCA2 functions are only beginning to emerge.
HIV is a lentivirus characterized by the formation of its mature core. Visualization and structural examination of HIV requires purification of virions to high concentrations. The yield and integrity of these virions are crucial for ensuring a uniform representation of all viral particles in subsequent analyses.
