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991.
Membrane contact sites, where two organelles are in close proximity, are critical regulators of cellular membrane homeostasis, with roles in signaling, lipid metabolism, and ion dynamics. A growing catalog of specialized lipid transfer proteins carry out lipid exchange at these sites. Currently characterized eukaryotic lipid transport proteins are shuttles that typically extract a single lipid from the membrane of the donor organelle, solubilize it during transport through the cytosol, and deposit it in the acceptor organelle membrane. Here, we highlight the recently identified chorein_N family of lipid transporters, including the Vps13 proteins and the autophagy protein Atg2. These are elongated proteins that, distinct from previously characterized transport proteins, bind tens of lipids at once. They feature an extended channel, most likely lined with hydrophobic residues. We discuss the possibility that they are not shuttles but instead are bridges between membranes, with lipids traversing the cytosol via the hydrophobic channel. 相似文献
992.
Identification of the replication region of Lactobacillus acidophilus plasmid pLA103 总被引:1,自引:0,他引:1
Kazuo Kanatani Takatsugu Tahara Masao Oshimura Keiji Sano chisae Umezawa 《FEMS microbiology letters》1995,133(1-2):127-130
Abstract The structure of the region necessary for replication of the plasmid pLA103 from Lactobacillus acidophilus TK8912 has been characterized. Sequence analysis revealed that the replication region contained an open reading frame (OrfA) encoding a 282-amino acid peptide preceded by a 22-bp tandem repeat sequence region. The predicted OrfA protein showed homology to the replication protein of a plasmid from Pediococcus halophilus . The plasmid containing the repeat sequence region preceding OrfA was able to replicate in the Lactobacillus host when provided with OrfA in trans , suggesting that the repeat sequence region contains the origin sequence essential for the pLA103 replication. 相似文献
993.
Janet Leatherwood 《Current opinion in cell biology》1998,10(6):742-748
Recent research has focused on proteins important for early steps in replication in eukaryotes, and particularly on Cdc6/Cdc18, the MCMs, and Cdc45. Although it is still unclear exactly what role these proteins play, it is possible that they are analogous to initiation proteins in prokaryotes. One specific model is that MCMs form a hexameric helicase at replication forks, and Cdc6/Cdc18 acts as a ‘clamp-loader’ required to lock the MCMs around DNA. The MCMs appear to be the target of Cdc7-Dbf4 kinase acting at individual replication origins. Finally, Cdc45 interacts with MCMs and may shed light on how cyclin-dependent kinases activate DNA replication. 相似文献
994.
The cell cycle in plant development 总被引:5,自引:1,他引:4
DENNIS FRANCIS 《The New phytologist》1992,122(1):1-20
995.
D Thirumal Kumar Maryam Umer Niazullah Sadia Tasneem E Judith B Susmita C George Priya Doss E Selvarajan Hatem Zayed 《Journal of cellular biochemistry》2019,120(3):3491-3505
Pompe disease is an autosomal recessive lysosomal storage disease caused by acid α-glucosidase (GAA) deficiency, resulting in intralysosomal accumulation of glycogen, including cardiac, skeletal, and smooth muscle cells. The GAA gene is located on chromosome 17 (17q25.3), the GAA protein consists of 952 amino acids; of which 378 amino acids (347-726) falls within the catalytic domain of the protein and comprises of active sites (518 and 521) and binding sites (404, 600, 616, and 674). In this study, we used several computational tools to classify the missense mutations in the catalytic domain of GAA for their pathogenicity and stability. Eight missense mutations (R437C, G478R, N573H, Y575S, G605D, V642D, L705P, and L712P) were predicted to be pathogenic and destabilizing to the protein structure. These mutations were further subjected to phenotyping analysis using SNPeffect 4.0 to predict the chaperone binding sites and structural stability of the protein. The mutations R437C and G478R were found to compromise the chaperone-binding activity with GAA. Molecular docking analysis revealed that the G478R mutation to be more significant and hinders binding to the DNJ (Miglustat) compared with the R437C. Further molecular dynamic analysis for the two mutations demonstrated that the G478R mutation was acquired higher deviation, fluctuation, and lower compactness with decreased intramolecular hydrogen bonds compared to the mutant R437C. These data are expected to serve as a platform for drug design against Pompe disease and will serve as an ultimate tool for variant classification and interpretations. 相似文献
996.
《Molecular cell》2020,77(1):17-25.e5
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997.
《L'Anthropologie》2022,126(2):103023
The Upper Pleistocene in Tunisia is characterized by cyclic climatic alternations between rainy and arid phases. The steppic landscape occupies a large area of the country, in particular in the Centre and the South. Even during the humid phases, the savannah landscape still dominant. The Upper Pleistocene prehistoric sites in Tunisia, such as Oued el Akarit, Aïn Mhrotta, Oued el Bey, El Guettar, Aïn Métherchem and Aïn el Guettar, which are the subject of this study, are all open-air sites, located mainly in Central and southern Tunisia, usually to the south of the springs that are still functioning today, or on the border of the wadis from which their names derive. Prehistoric occupations and human behavior are mainly subject to the climatic shifts occurred during the Upper Pleistocene. 相似文献
998.
《Journal of molecular biology》2022,434(17):167692
While the accelerating quest for precision medicine requires new individually targeting and selective drugs, and the ability to work with so-called undruggable targets, the realm of allosteric drugs meeting this need remains largely uncharted. Generalizing the observations on two major drug targets with widely observed inherent allostery, GPCRs and kinases, we describe and discuss basic allosteric modes of action that are universally applicable in all types of structures and functions. Using examples of Class A GPCRs and CMGC protein kinases, we show how Allosteric Signalling and Probing Fingerprints can be used to identify potential allosteric sites and reveal effector-leads that may serve as a starting point for the development of allosteric drugs targeting these regulatory sites. A set of distinct characteristics of allosteric ligands was established, which highlights the versatility of their design and make them advantageous before their orthosteric counterparts in personalized medicine. We argue that rational design of allosteric drugs should begin with the search for latent sites or design of non-natural binding sites followed by fragment-based design of allosteric ligands and by the mutual adjustment of the site-ligand pair in order to achieve required drug efficacy. On the basis of the perturbative nature and reversibility of allosteric communication, we propose a generic protocol for computational design of allosteric effectors, enabling also the allosteric tuning of biologics, in obtaining allosteric control over protein functions. 相似文献
999.
1000.