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Search results for: Translocase

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#33084070   2020/10/20 To Up

Novel IM-associated protein Tim54 plays a role in the mitochondrial import of internal signal-containing proteins in Trypanosoma brucei.

The translocase of the mitochondrial inner membrane (TIM) imports most of the nucleus-encoded proteins that are destined for the matrix, inner membrane (IM), and the intermembrane space (IMS). Trypanosoma brucei, the infectious agent for African trypanosomiasis, possesses a unique TIM complex consisting of several novel proteins in association with a relatively conserved protein TbTim17. Tandem affinity purification of the TbTim17 protein complex revealed TbTim54 as a potential component of this complex.
Ujjal K Singha, Anuj Tripathi, Joseph T Smith, Linda Quinones, Aparajita Saha, Tanusree Singha, Minu Chaudhuri

2355 related Products with: Novel IM-associated protein Tim54 plays a role in the mitochondrial import of internal signal-containing proteins in Trypanosoma brucei.

25mg1mg50 2 Pieces/Box100 μg100 μg1. Set100 μg2 Pieces/Box50 100 μg100 units

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#33083003   2020/09/29 To Up

Atomic structure of human TOM core complex.

The translocase of the outer mitochondrial membrane (TOM) complex is the main entry gate for mitochondrial precursor proteins synthesized on cytosolic ribosomes. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the dimeric human TOM core complex (TOM-CC). Two Tom40 β-barrel proteins, connected by two Tom22 receptor subunits and one phospholipid, form the protein-conducting channels. The small Tom proteins Tom5, Tom6, and Tom7 surround the channel and have notable configurations. The distinct electrostatic features of the complex, including the pronounced negative interior and the positive regions at the periphery and center of the dimer on the intermembrane space (IMS) side, provide insight into the preprotein translocation mechanism. Further, two dimeric TOM complexes may associate to form tetramer in the shape of a parallelogram, offering a potential explanation into the unusual structural features of Tom subunits and a new perspective of viewing the import of mitochondrial proteins.
Wenhe Wang, Xudong Chen, Laixing Zhang, Jingbo Yi, Qingxi Ma, Jian Yin, Wei Zhuo, Jinke Gu, Maojun Yang

2066 related Products with: Atomic structure of human TOM core complex.

100 ul500100ug Lyophilized1 IU2

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#33038868   2020/09/19 To Up

Suppression of up-regulated LXRα by silybin ameliorates experimental rheumatoid arthritis and abnormal lipid metabolism.

As dysregulation of immunometabolism plays a key role in the immunological diseases, dyslipidemia frequently observed in rheumatoid arthritis (RA) patients (60%) is associated with the disease activity and has been considered as the potential target of anti-inflammatory strategy. However, targeting of metabolic events to develop novel anti-inflammatory therapeutics are far from clear as well as the mechanism of dyslipidemia in RA.
Ying Xie, Sen-Ling Feng, Chu-Tian Mai, Yan-Fang Zheng, Hui Wang, Zhong-Qiu Liu, Hua Zhou, Liang Liu

2992 related Products with: Suppression of up-regulated LXRα by silybin ameliorates experimental rheumatoid arthritis and abnormal lipid metabolism.

100ul1,000 tests200ug 72 tests1 mg100 assays1000 tests100ug100ug1000 25 mg

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#33035511   2020/10/07 To Up

Mechanisms and pathways of mitochondrial outer membrane protein biogenesis.

Outer membrane proteins integrate mitochondria into the cellular environment. They warrant exchange of small molecules like metabolites and ions, transport proteins into mitochondria, form contact sites to other cellular organelles for lipid exchange, constitute a signaling platform for apoptosis and inflammation and mediate organelle fusion and fission. The outer membrane contains two types of integral membrane proteins. Proteins with a transmembrane β-barrel structure and proteins with a single or multiple α-helical membrane spans. All outer membrane proteins are produced on cytosolic ribosomes and imported into the target organelle. Precursors of β-barrel and α-helical proteins are transported into the outer membrane via distinct import routes. The translocase of the outer membrane (TOM complex) transports β-barrel precursors across the outer membrane and the sorting and assembly machinery (SAM complex) inserts them into the target membrane. The mitochondrial import (MIM) complex constitutes the major integration site for α-helical embedded proteins. The import of some MIM-substrates involves TOM receptors, while others are imported in a TOM-independent manner. Remarkably, TOM, SAM and MIM complexes dynamically interact to import a large set of different proteins and to coordinate their assembly into protein complexes. Thus, protein import into the mitochondrial outer membrane involves a dynamic platform of protein translocases.
Arushi Gupta, Thomas Becker

1736 related Products with: Mechanisms and pathways of mitochondrial outer membrane protein biogenesis.

0.1 ml100ug96T100ug500 250 0.1 mg 100ul 100ul100ul 100ul1 kit

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#33020301   2020/10/05 To Up

Modular and coordinated activity of AAA+ active sites in the double-ring ClpA unfoldase of the ClpAP protease.

ClpA is a hexameric double-ring AAA+ unfoldase/translocase that functions with the ClpP peptidase to degrade proteins that are damaged or unneeded. How the 12 ATPase active sites of ClpA, 6 in the D1 ring and 6 in the D2 ring, work together to fuel ATP-dependent degradation is not understood. We use site-specific cross-linking to engineer ClpA hexamers with alternating ATPase-active and ATPase-inactive modules in the D1 ring, the D2 ring, or both rings to determine if these active sites function together. Our results demonstrate that D2 modules coordinate with D1 modules and ClpP during mechanical work. However, there is no requirement for adjacent modules in either ring to be active for efficient enzyme function. Notably, ClpAP variants with just three alternating active D2 modules are robust protein translocases and function with double the energetic efficiency of ClpAP variants with completely active D2 rings. Although D2 is the more powerful motor, three or six active D1 modules are important for high enzyme processivity, which depends on D1 and D2 acting coordinately. These results challenge sequential models of ATP hydrolysis and coupled mechanical work by ClpAP and provide an engineering strategy that will be useful in testing other aspects of ClpAP mechanism.
Kristin L Zuromski, Robert T Sauer, Tania A Baker

2769 related Products with: Modular and coordinated activity of AAA+ active sites in the double-ring ClpA unfoldase of the ClpAP protease.

1500 Units

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#33007515   2020/09/17 To Up

Envisioning how the prototypic molecular machine TFIIH functions in transcription initiation and DNA repair.

Critical for transcription initiation and bulky lesion DNA repair, TFIIH provides an exemplary system to connect molecular mechanisms to biological outcomes due to its strong genetic links to different specific human diseases. Recent advances in structural and computational biology provide a unique opportunity to re-examine biologically relevant molecular structures and develop possible mechanistic insights for the large dynamic TFIIH complex. TFIIH presents many puzzles involving how its two SF2 helicase family enzymes, XPB and XPD, function in transcription initiation and repair: how do they initiate transcription, detect and verify DNA damage, select the damaged strand for incision, coordinate repair with transcription and cell cycle through Cdk-activating-kinase (CAK) signaling, and result in very different specific human diseases associated with cancer, aging, and development from single missense mutations? By joining analyses of breakthrough cryo-electron microscopy (cryo-EM) structures and advanced computation with data from biochemistry and human genetics, we develop unified concepts and molecular level understanding for TFIIH functions with a focus on structural mechanisms. We provocatively consider that TFIIH may have first evolved from evolutionary pressure for TCR to resolve arrested transcription blocks to DNA replication and later added its key roles in transcription initiation and global DNA repair. We anticipate that this level of mechanistic information will have significant impact on thinking about TFIIH, laying a robust foundation suitable to develop new paradigms for DNA transcription initiation and repair along with insights into disease prevention, susceptibility, diagnosis and interventions.
Susan E Tsutakawa, Chi-Lin Tsai, Chunli Yan, Amer Bralić, Walter J Chazin, Samir M Hamdan, Orlando D Schärer, Ivaylo Ivanov, John A Tainer

2298 related Products with: Envisioning how the prototypic molecular machine TFIIH functions in transcription initiation and DNA repair.

2 Pieces/Box1100 1 mg

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#33007364   2020/09/29 To Up

Involvement of CYP2E1-ROS-CD36/DGAT2 axis in the pathogenesis of VPA-induced hepatic steatosis in vivo and in vitro.

Valproic acid (VPA) is a widely prescribed antiepileptic drug, which may cause steatosis in the liver. Oxidative stress is associated with the progression of VPA-induced hepatic steatosis. However, the potential mechanisms are not fully understood. In this study, we demonstrated the involvement of CYP2E1-ROS-CD36/DGAT2 axis in the pathogenesis of VPA-induced hepatic steatosis in vitro and in vivo. First, VPA treatment (500 mg/kg in mice, 5 mM in LO cells) induced hepatic steatosis and enhanced reactive oxidative stress (ROS) level, and ROS scavenger, N-acetyl-L-cysteine (NAC, 200 mg/kg in mice, 1 mM in LO cells) reversed the changes. Next, we observed the enhanced expression and enzymatic activity of cytochrome P450 2E1 (CYP2E1) in VPA-treated mice and LO cells. Importantly, VPA-induced ROS accumulation and hepatic steatosis were attenuated when CYP2E1 was inhibited using CYP2E1 inhibitor, diallyl sulfide (DAS, 100 mg/kg in mice, 1 mM in LO cells) or in CYP2E1-knockdown cell line, suggesting that CYP2E1 plays a potential role in ROS production following hepatic steatosis. Furthermore, gene expression analysis showed that the mRNA levels of cluster of differentiation 36 (CD36), a fatty acid translocase protein and distinct diacylglycerol acyltransferase 2 (DGAT2) were significantly upregulated in mice and LO cells after VPA treatment, while the change was alleviated by NAC and DAS. Meanwhile, time course experiments demonstrated that the increase of CYP2E1 level occurred earlier than that of ROS, CD36 and DGAT2, and ROS generation preceded the onset of hepatic steatosis. Taken together, VPA treatment enhances the expression and enzymatic activity of CYP2E1, which promotes ROS production and then causes CD36 and DGAT2 overproduction and hepatic steatosis in mice and LO cells, which provides a novel insight into VPA-induced hepatic steatosis.
Linfeng Ma, Yani Wang, Xue Chen, Limei Zhao, Yingjie Guo

1329 related Products with: Involvement of CYP2E1-ROS-CD36/DGAT2 axis in the pathogenesis of VPA-induced hepatic steatosis in vivo and in vitro.

50 ul96 tests196T1 mg100 μg 100ul5ug

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#32997992   // To Up

Transport Cycle of Plasma Membrane Flippase ATP11C by Cryo-EM.

ATP11C, a plasma membrane phospholipid flippase, maintains the asymmetric distribution of phosphatidylserine accumulated in the inner leaflet. Caspase-dependent inactivation of ATP11C is essential for an apoptotic "eat me" signal, phosphatidylserine exposure, which prompts phagocytes to engulf cells. We show six cryo-EM structures of ATP11C at 3.0-4.0 Å resolution in five different states of the transport cycle. A structural comparison reveals phosphorylation-driven domain movements coupled with phospholipid binding. Three structures of phospholipid-bound states visualize phospholipid translocation accompanied by the rearrangement of transmembrane helices and an unwound portion at the occlusion site, and thus they detail the basis for head group recognition and the locality of the protein-bound acyl chains in transmembrane grooves. Invariant Lys880 and the surrounding hydrogen-bond network serve as a pivot point for helix bending and precise P domain inclination, which is crucial for dephosphorylation. The structures detail key features of phospholipid translocation by ATP11C, and a common basic mechanism for flippases is emerging.
Hanayo Nakanishi, Tomohiro Nishizawa, Katsumori Segawa, Osamu Nureki, Yoshinori Fujiyoshi, Shigekazu Nagata, Kazuhiro Abe

2393 related Products with: Transport Cycle of Plasma Membrane Flippase ATP11C by Cryo-EM.

1.00 flask0.1 ml96T 72 tests200 ug50 µg22 Membrane supply

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#32982800   2020/08/31 To Up

Inhibition of miR-27b Regulates Lipid Metabolism in Skeletal Muscle of Obese Rats During Hypoxic Exercise by Increasing PPARγ Expression.

Hypoxic exercise may represent a novel therapeutic strategy to reduce and prevent obesity through the regulation of lipid metabolism. During hypoxic exercise, the targeting of peroxisome proliferator-activated receptor gamma (PPARγ) by miR-27b has been proposed to be one of the mechanisms involved in the modulation of lipid metabolism. We have previously shown that miR-27b can repress PPARγ and lipid metabolism-associated factors, thereby affecting lipid metabolism during hypoxic exercise in a rat model of obesity. In the current study, we aimed to confirm the role of miR-27b in the regulation of lipid metabolism. First, miR-27b expression was either upregulated or downregulated through the injection of adeno-associated virus (AAV) 9 containing a miR-27b expression cassette or miR-27b-3p inhibitor, respectively, into the right gastrocnemius muscle of obese rats. The rats were then subjected to a 4-week program of hypoxic exercise, and a series of parameters related to lipid metabolism were systematically evaluated, including body composition, blood lipid levels, miR-27b RNA levels, and mRNA and protein levels of PPARγ and those of its downstream lipid metabolism-associated factors. No significant differences were found in body composition between rats expressing different levels of miR-27b. However, regarding blood lipids, miR-27b overexpression led to increased concentrations of triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and free fatty acids (FFAs), while inhibition of miR-27b decreased the total cholesterol (TC) level and increased that of high-density lipoprotein cholesterol (HDL-C). At the mRNA level, miR-27b overexpression downregulated the expression of γ, but upregulated that of lipid metabolism-associated factors such as heart-type fatty acid-binding protein (H-FABP), fatty acid transport protein 1 (FATP1), adipose triglyceride lipase (ATGL), and lipoprotein lipase (LPL), whereas miR-27b inhibition elicited the opposite effect; however, inhibition of miR-27b led to elevated cholesterol 7 alpha-hydroxylase (CYP7A1) and fatty acid translocase 36 (CD36) levels. Similarly, at the protein level, miR-27b overexpression promoted a decrease in the concentration of PPARγ, whereas miR-27b inhibition led to an increase in PPARγ levels, as well as those of CYP7A1, CD36, ATGL, and LPL. Overall, our results indicated that hypoxic exercise regulates lipid metabolism via the miR-27b/PPARγ pathway and modulates ATGL and LPL expression through inducing their post-transcriptional modifications.
Xuebing Wang, Yingli Lu, Lei Zhu, Haibo Zhang, Lianshi Feng

2486 related Products with: Inhibition of miR-27b Regulates Lipid Metabolism in Skeletal Muscle of Obese Rats During Hypoxic Exercise by Increasing PPARγ Expression.

48 assays 100ul96 tests96 wells96 assays 200ul96 wells48 assays

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