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31.
Higher‐order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle 下载免费PDF全文
Arjen J Jakobi Abul K Tarafder Yury S Bykov Andrea Picco Wanda Kukulski Jan Kosinski Wim JH Hagen Arvind C Ravichandran Matthias Wilmanns Marko Kaksonen John AG Briggs Carsten Sachse 《EMBO reports》2016,17(7):1044-1060
Selective autophagy is the mechanism by which large cargos are specifically sequestered for degradation. The structural details of cargo and receptor assembly giving rise to autophagic vesicles remain to be elucidated. We utilize the yeast cytoplasm‐to‐vacuole targeting (Cvt) pathway, a prototype of selective autophagy, together with a multi‐scale analysis approach to study the molecular structure of Cvt vesicles. We report the oligomeric nature of the major Cvt cargo Ape1 with a combined 2.8 Å X‐ray and negative stain EM structure, as well as the secondary cargo Ams1 with a 6.3 Å cryo‐EM structure. We show that the major dodecameric cargo prApe1 exhibits a tendency to form higher‐order chain structures that are broken upon interaction with the receptor Atg19 in vitro. The stoichiometry of these cargo–receptor complexes is key to maintaining the size of the Cvt aggregate in vivo. Using correlative light and electron microscopy, we further visualize key stages of Cvt vesicle biogenesis. Our findings suggest that Atg19 interaction limits Ape1 aggregate size while serving as a vehicle for vacuolar delivery of tetrameric Ams1. 相似文献
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33.
Lack of geographic variation in anonymous nuclear polymorphisms in the American oyster, Crassostrea virginica 总被引:1,自引:0,他引:1
Comparing geographic variation of noncoding nuclear DNA polymorphisms,
which presumably are neutral to natural selection, with geographic
variation of allozymes is potentially a good way to detect the effects of
selection on allozyme polymorphisms. A previous study of four anonymous
nuclear markers in the American oyster, Crassostrea virginica, found
dramatic differences in allele frequency between the Gulf of Mexico and the
Atlantic Ocean. In contrast, 14 allozyme polymorphisms were fairly uniform
in frequency between the two areas. This led to the conclusion that all of
the allozyme polymorphisms were kept uniform in frequency by balancing
selection. To test the robustness of this pattern, six additional anonymous
nuclear DNA polymorphisms were surveyed in oysters from Panacea, Fla, and
Charleston, S.C. on the Gulf and Atlantic coasts, respectively. Unlike the
previously studied DNA markers, the six DNA polymorphisms examined here
show geographic variation that is not significantly greater than that of
allozymes. The reason for the discrepancy between the two sets of DNA
polymorphisms is unclear.
相似文献
34.
Kim HY Moon HS Cao D Lee J Kevala K Jun SB Lovinger DM Akbar M Huang BX 《The Biochemical journal》2011,435(2):327-336
DHA (docosahexaenoic acid, C22:6,n-3) has been shown to promote neurite growth and synaptogenesis in embryonic hippocampal neurons, supporting the importance of DHA known for hippocampus-related learning and memory function. In the present study, we demonstrate that DHA metabolism to DEA (N-docosahexaenoylethanolamide) is a significant mechanism for hippocampal neuronal development, contributing to synaptic function. We found that a fatty acid amide hydrolase inhibitor URB597 potentiates DHA-induced neurite growth, synaptogenesis and synaptic protein expression. Active metabolism of DHA to DEA was observed in embryonic day 18 hippocampal neuronal cultures, which was increased further by URB597. Synthetic DEA promoted hippocampal neurite growth and synaptogenesis at substantially lower concentrations in comparison with DHA. DEA-treated neurons increased the expression of synapsins and glutamate receptor subunits and exhibited enhanced glutamatergic synaptic activity, as was the case for DHA. The DEA level in mouse fetal hippocampi was altered according to the maternal dietary supply of n-3 fatty acids, suggesting that DEA formation is a relevant in vivo process responding to the DHA status. In conclusion, DHA metabolism to DEA is a significant biochemical mechanism for neurite growth, synaptogenesis and synaptic protein expression, leading to enhanced glutamatergic synaptic function. The novel DEA-dependent mechanism offers a new molecular insight into hippocampal neurodevelopment and function. 相似文献
35.
Role of HLA DRB1*15 and HLA DRB1*16alleles in the genetic susceptibility to develop systemic lupus erythematosus (SLE) after Chikungunya and Zika viruses infection in México 下载免费PDF全文
Sepúlveda-Delgado J Danis-Lozano R Ocaa-Sibilla MJ Ramirez-Valdespino JC Cetina-Díaz JH Bulos-Rodriguez P Hernández-Doo S Ruiz-Gómez D García R Juárez-Nicolás F Tevera-Gamboa MG Vera-Lastra OL Jara LJ Canseco-Avila LM Dominguez-Arrevillaga S Trujillo-Murillo K Julio Granados J 《Blood and Genomics》2018,2(4):233-236
Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous disease particularly prevalent in Mexico. Althoughits etiology is unknown, genetic factors strongly influence its presenceas well as triggering factors, such as viral infections, including Cytomegalovirus and Epstein-Barr virus. Here,the study presents the appearance of de novoSLE (patients who did not present SLE before de virus infection, corroborated by serological analysis and negative for antinuclear antibodies) cases in Mexicans who live near the southern border of Mexico, who presented clinical symptoms of arthritic, hematological, mucocutaneous and renal SLE, after Zika and/ or Chikungunya virus infection. Low resolution class Ⅱ HLA typing was performed, which found a significantly increased frequency of HLA DRB1*02 (15 and 16)when compared to a group of 99 healthy individuals (P =0.001, OR=4.5, IC95% 1.8~11.0). All the patients were diagnosed with SLE 1 to 3 years after being confirmed with the Zika, and/or Chikungunya infection. At the point of acute viral infection, none of the patients presented clinical signs or symptoms of autoimmunity or were negative for antinuclear antibodies. In genetically susceptible individuals, Zika and Chikungunya viral infection can trigger SLE. 相似文献
36.
Background
Protein remote homology detection is a central problem in computational biology. Most recent methods train support vector machines to discriminate between related and unrelated sequences and these studies have introduced several types of kernels. One successful approach is to base a kernel on shared occurrences of discrete sequence motifs. Still, many protein sequences fail to be classified correctly for a lack of a suitable set of motifs for these sequences. 相似文献37.
Umapathy Vidhya Rekha Rama Varadhachariyar Ponnulakshmi Rajagopal Puja Harie Priya JH Shazia Fathima Ramajayam Govindan Chella Perumal Palanisamy Vishnu Priya Veeraraghavan Selvaraj Jayaraman 《Bioinformation》2022,18(3):261
Natural remedies from medicinal plants are known to be effective and reliable appropriate medicine for illnesses. The current research examined Plectranthus amboinicus'' anti diabetic property by docking the bioactive compounds of certain target proteins. We document the molecular docking analysis of bioactive compounds from Plectranthus amboinicus with protein Glucokinase. Molecular docking experiments were carried out in PyRx software. Results of these docking experiments showed that most of the compounds showed very strong interaction with the target protein Glucokinase. Based on the scoring parameters we have selected best four compounds (Rutin, Salvianolic acid, Luteolin and Salvigenin) which showed very good docking score and hydrogen bond interaction for diabetics. 相似文献
38.
Substrate preference in phosphatidylserine biosynthesis for docosahexaenoic acid containing species 总被引:5,自引:0,他引:5
Neuronal membranes contain high levels of phosphatidylserine (PS) and docosahexaenoic acid (22:6n-3, DHA). In this study, substrate preference in PS synthesis was determined to gain insight on the biochemical basis for concentrating PS in neuronal membranes where 22:6n-3 is highly enriched. We first established an in vitro assay method using unilamellar vesicles (LUV) of deuterium-labeled substrates and reversed-phase HPLC/electrospray ionization (ESI) mass spectrometry. The PS production by the incubation of deuterium-labeled substrate and microsomal fractions was monitored. We found that tissue-specific substrate preference exists in PS synthesis. Microsomes from the cerebral cortex synthesized PS from 18:0,22:6-PC most favorably among the PC substrates tested, followed by 18:0,22:5-PC, resulting in the PC substrate preference in the order of 18:0,22:6 > 18:0,22:5 > 18:0,20:4 = 18:0,18:1. Liver microsomes also preferred 18:0,22:6-PC as the substrate in PS synthesis but did not use 18:0,22:5-PC favorably. The 18:0,22:5-PC species was converted to PS at the similar extent as 18:0,20:4- or 18:0,18:1-PC species in the liver. Both brain and liver microsomes showed a preference for 18:0 over 16:0 as the sn-1 fatty acid. From these data it was deduced that preferential conversion of 18:0,22:6-PC to the corresponding PS species is at least partly responsible for concentrating PS in neuronal tissues where 22:6n-3 is particularly abundant. The distinctive preference for 18:0,22:5-PS observed with brain microsomes may help to maintain PS at a high level in the brain when 22:6n-3 is replaced by 22:5n-3 as in the case of n-3 fatty acid deficiency. 相似文献
39.
A method has been developed to determine the substrate preference in phosphatidylserine decarboxylation (PSD), the process by which phosphatidylserine is converted to phosphatidylethanolamine (PE) in the mitochondria. The in vitro assay utilized liposomes containing deuterium-labeled PS molecular species incubated with liver and brain cortex mitochondria, and the conversion of PS to the corresponding PE species was monitored by electrospray ionization mass spectrometry in conjunction with reversed-phase liquid chromatography. Employing this approach we were able to establish for the first time that there exists a substrate preference in PSD in liver (18:0,18:1 > or = 18:0,22:6 > 18:0,20:4-PS) and brain cortex (18:0,22:6 > 18:0,18:1 > 18:0,20:4-PS). The observed PSD molecular species preference, however, did not reflect the mitochondrial PE profile, suggesting that selectivity in other processes such as de novo PE synthesis, intracellular transport of phospholipid molecules, or remodeling by deacylation-reacylation may be important contributors in maintaining a specific lipid profile in mitochondria. 相似文献
40.