29 research outputs found

    The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA

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    Tfam (transcription factor A, mitochondrial), a DNA-binding protein with tandem high-mobility group (HMG)-box domains, has a central role in the expression, maintenance and organization of the mitochondrial genome. It activates transcription from mitochondrial promoters and organizes the mitochondrial genome into nucleoids. Using X-ray crystallography, we show that human Tfam forces promoter DNA to undergo a U-turn, reversing the direction of the DNA helix. Each HMG-box domain wedges into the DNA minor groove to generate two kinks on one face of the DNA. On the opposite face, a positively charged α-helix serves as a platform to facilitate DNA bending. The structural principles underlying DNA bending converge with those of the unrelated HU family proteins, which have analogous architectural roles in organizing bacterial nucleoids. The functional importance of this extreme DNA bending is promoter specific and seems to be related to the orientation of Tfam on the promoters

    Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation

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    TFAM (transcription factor A, mitochondrial) is a DNA-binding protein that activates transcription at the two major promoters of mitochondrial DNA (mtDNA)—the light strand promoter (LSP) and the heavy strand promoter 1 (HSP1). Equally important, it coats and packages the mitochondrial genome. TFAM has been shown to impose a U-turn on LSP DNA; however, whether this distortion is relevant at other sites is unknown. Here we present crystal structures of TFAM bound to HSP1 and to nonspecific DNA. In both, TFAM similarly distorts the DNA into a U-turn. Yet, TFAM binds to HSP1 in the opposite orientation from LSP explaining why transcription from LSP requires DNA bending, whereas transcription at HSP1 does not. Moreover, the crystal structures reveal dimerization of DNA-bound TFAM. This dimerization is dispensable for DNA bending and transcriptional activation but is important in DNA compaction. We propose that TFAM dimerization enhances mitochondrial DNA compaction by promoting looping of the DNA

    Ultra-wide Spectral Bandwidth and Enhanced Absorption in a Metallic Compound Grating Covered by Graphene Monolayer

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    Graphene, a two-dimensional monatomic layer of carbon material, has demonstrated as a good candidate for applications of ultrafast photodetectors, transistors, transparent electrodes, and biosensing. Recently, many studies have shown that using metallic deep gratings could enhance the absorptance of graphene of 2.3% up to 80% in the near infrared region for applications in photon detection. This paper presents utilizing a nanograting structure, namely, a compound metallic grating could greatly enhance the absorptance of graphene to 100% and widen its spectral bandwidth to 600 nm, which are greater than those of previous work. The study also showed that the absorptance spectrum is insensitive to angles of incidence. Furthermore, the proposed graphene-covered compound grating might bring a lot of benefits for graphene designs-based optical and optoelectronic devices

    Associations of Underlying Health Conditions With Anxiety and Depression Among Outpatients: Modification Effects of Suspected COVID-19 Symptoms, Health-Related and Preventive Behaviors

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    Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB).Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18–85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety.Results: People with UHC had higher odds of depression (OR = 2.11; p < 0.001) and anxiety (OR = 2.86; p < 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p < 0.001); and were significantly lower for those had UHC and interacted with “unchanged/more” physical activity (p < 0.001), or “unchanged/more” drinking (p < 0.001 for only anxiety), or “unchanged/healthier” eating (p < 0.001), and high PB score (p < 0.001), as compared to those without UHC and without S-COVID-19-S, “never/stopped/less” physical activity, drinking, “less healthy” eating, and low PB score, respectively.Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors

    Dynamics of mitochondria and mitochondrial DNA

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    Mitochondria are dynamic organelles that fuse and divide. The study of mice lacking these dynamic processes has revealed physiological roles for mitochondrial dynamics. Recent studies indicate a link between mitochondrial dynamics and mitochondrial DNA (mtDNA) stability. To study this issue, we have performed structural studies on Tfam, a DNA binding protein that plays a central role in expression, maintenance, and organization of the mitochondrial genome. It activates transcription from mitochondrial promoters and organizes the mitochondrial genome into nucleoids. Using X-ray crystallography, we show that human Tfam forces promoter DNA to undergo a U-turn, reversing the direction of the DNA helix. The structural principles underlying DNA bending converge with those of the unrelated HU family proteins, which play analogous architectural roles in organizing bacterial nucleoids
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