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1.
《Journal of molecular biology》2021,433(15):167098
MPV17 is an integral inner mitochondrial membrane protein, whose loss-of-function is linked to the hepatocerebral form of the mitochondrial-DNA-depletion syndrome, leading to a tissue-specific reduction of mitochondrial DNA and organ failure in infants. Several disease-causing mutations in MPV17 have been identified and earlier studies with reconstituted protein suggest that MPV17 forms a high conductivity channel in the membrane. However, the molecular and structural basis of the MPV17 functionality remain only poorly understood. In order to make MPV17 accessible to high-resolution structural studies, we here present an efficient protocol for its high-level production in E. coli and refolding into detergent micelles. Using biophysical and NMR methods, we show that refolded MPV17 in detergent micelles adopts a compact structure consisting of six membrane-embedded α-helices. Furthermore, we demonstrate that MPV17 forms oligomers in a lipid bilayer that are further stabilized by disulfide-bridges. In line with these findings, MPV17 could only be inserted into lipid nanodiscs of 8–12 nm in diameter if intrinsic cysteines were either removed by mutagenesis or blocked by chemical modification. Using this nanodisc reconstitution approach, we could show that disease-linked mutations in MPV17 abolish its oligomerization properties in the membrane. These data suggest that, induced by oxidative stress, MPV17 can alter its oligomeric state from a properly folded monomer to a disulfide-stabilized oligomeric pore which might be required for the transport of metabolic DNA precursors into the mitochondrial matrix to compensate for the damage caused by reactive oxygen species. 相似文献
2.
Myoglobin (Mb) is the classic vertebrate oxygen-binding protein present in aerobic striated muscles. It functions principally in oxygen delivery and provides muscle with its characteristic red colour. Members of the Antarctic icefish family (Channichthyidae) are widely thought to be extraordinary for lacking cardiac Mb expression, a fact that has been attributed to their low metabolic rate and unusual evolutionary history. Here, we report that cardiac Mb deficit, associated with pale heart colour, has evolved repeatedly during teleost evolution. This trait affects both gill- and air-breathing species from temperate to tropical habitats across a full range of salinities. Cardiac Mb deficit results from total pseudogenization in three-spined stickleback and is associated with a massive reduction in mRNA level in two species that evidently retain functional Mb. The results suggest that near or complete absence of Mb-assisted oxygen delivery to heart muscle is a common facet of teleost biodiversity, even affecting lineages with notable oxygen demands. We suggest that Mb deficit may affect how different teleost species deal with increased tissue oxygen demands arising under climate change. 相似文献
3.
《Free radical research》2013,47(1-3):3-10
The role of free radicals and active states of oxygen in human cancer is as yet unresolved. Various lines of evidence provide strong but inferential evidence that free radical reactions can be of crucial importance in certain carcinogenic mechanisms. A central point in considering free radical reactions in carcinogenesis is that human cancer is really a group of highly diverse diseases for which the initial causation and the progression to clinical disease occur through a wide variety of mechanisms. Furthermore, for many human cancers it appears that there are alternate pathways capable of tumor initiation and tumor progression. While for certain of these pathways free radical reactions appear necessary, it is unlikely that there are human cancers for which free radicals, or any other mechanism, are sufficient for the entire processbeginning with the genetic alteration leading to a somatic mutation and eventually resulting in clinically overt disease. It is crucial that we view free radical reactions as aong a panoply of mechanisms leading to human cancer, and consider research about the role of free radicals in cancer as opportunities to prevent the initiation or progression of human cancer. 相似文献
4.
《Molecular & cellular proteomics : MCP》2020,19(1):142-154
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- •Flow cytometry analysis is used to isolate ASC speck(+) NPC cells.
- •Proteome analysis of ASC speck(+) NPC cells reveals enriched mitochondrial OxPhos proteins.
- •OxPhos proteins mediate NLRP3 inflammasome activation through mtROS.
- •OxPhos proteins, NDUFB8 and ATP5B are correlated with NPC local recurrence.
5.
Heat stress reduces maize yield and several lines of evidence suggest that the heat lability of maize endosperm ADP-glucose pyrophosphorylase (AGPase) contributes to this yield loss. AGPase catalyzes a rate-limiting step in starch synthesis. Herein, we present a novel maize endosperm AGPase small subunit variant, termed BT2-TI that harbors a single amino acid change of residue 462 from threonine to isoleucine. The mutant was isolated by random mutagenesis and heterologous expression in a bacterial system. BT2-TI exhibits enhanced heat stability compared to wildtype maize endosperm AGPase.The TI mutation was placed into another heat-stable small subunit variant, MP. MP is composed of sequences from the maize endosperm and the potato tuber small subunit. The MP-TI small subunit variant exhibited greater heat stability than did MP. Characterization of heat stability as well as kinetic and allosteric properties suggests that MP-TI may lead to increased starch yield when expressed in monocot endosperms. 相似文献
6.
Summary Between 3 Nov. 1983 and 9 Apr. 1984, six applications of fertiliser N (ammonium, nitrate or urea) were given to four autumn
sown (26 Oct. 1983)Vicia faba L cultivars, Banner Winter (BW) and Maris Beagle (MBg), cold tolerant cultivars normally sown in the autumn, and Herz Freya
(HF) and Maris Bead (MBd), cold sensitive cultivars more commonly sown in the spring. The effects of additional N were determined
by comparison with plants given zero-N (controls).
Application of N, regardless of form, had no effect on % emergence at the first sampling (15 Dec. 1983); >90% for BW, MBg
and HF, but only 40–60% for MBd. At this time the dry weight, carbon content and nitrogen content of all cultivars was approximately
20% less than that of the seed on planting. No more plants emerged after 15 Dec. 1983. Between 15 Dec. 1983 and 20 Feb. 1984,
all cultivars, regardless of N treatment, showed little change in dry weight, carbon content and nitrogen content but the
proportion of total plant dry weight, carbon content and nitrogen content in the cotyledons decreased while the proportions
in root, stem and leaf tissue increased. On 20 Feb. 1984 there were no N effects. All cultivars but especially BW and MBg,
showed progressive increases in dry weight, carbon content and nitrogen content during the period 20 Feb. 1984 to 8 May 1984.
Pooled results for all four cultivars indicated that on 8 May 1984, plants given ammonium and urea had a greater dry weight,
carbon content and nitrogen content than controls.
At harvest (1–3 Sep. 1984), BW and MBg outyielded (g dw seed m−2) HF and MBd. Pooled results for all cultivars indicated that application of N regardless of form gave increased yield and
an increased N concentration (mg N g−1 dw) in the seed. 相似文献
7.
Gamze Gülez 《Journal of microbiological methods》2010,82(3):324-326
To study bacterial behavior under varying hydration conditions similar to surface soil, we have developed a system called the Pressurized Porous Surface Model (PPSM). Thin liquid films created by imposing a matric potential of − 0.4 MPa impact gene expression and colony development in Pseudomonas putida. 相似文献
8.
Elena C. Guzman Alfonso Jimenez-Sanchez Elisha Orr Robert H. Pritchard 《Molecular & general genetics : MGG》1988,212(2):203-206
Summary A temperature shift-up accompanied by a reduction in RNA polymerase activity in Escherichia coli causes an increased rate of initiation leading to a 1.7- to 2.2-fold increase in chromosome copy number. A temperature shift-up without a reduction in polymerase activity induces only a transient non-scheduled initiation of chromosome replication caused by heat shock with no detectable effect on chromosome copy number. 相似文献
9.
Shashank Hambarde Chi-Lin Tsai Raj K. Pandita Albino Bacolla Anirban Maitra Vijay Charaka Clayton R. Hunt Rakesh Kumar Oliver Limbo Remy Le Meur Walter J. Chazin Susan E. Tsutakawa Paul Russell Katharina Schlacher Tej K. Pandita John A. Tainer 《Molecular cell》2021,81(14):2989-3006.e9
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10.
Antonis E. Koromilas 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(3):644-649
Cells employ pro-survival and pro-adaptive pathways to cope with different forms of environmental stress. When stress is excessive, and the damage caused by it is unsustainable, cells engage pro-death pathways, which are in place to protect the host from the deleterious effects of harmed cells. Two important pathways that determine the balance between survival and death of stressed cells are the integrated stress response (ISR) and the mammalian target of rapamycin (mTOR), both of which converge at the level of mRNA translation. The two pathways have established avenues of communication to control their activity and determine the fate of stressed cells in a context-dependent manner. The functional interplay between the ISR and mTOR may have significant ramifications in the development and treatment of human diseases such as diabetes, neurodegeneration and cancer. 相似文献