Geminiviruses encode additional small proteins with specific subcellular localizations and virulence function.
Ontology highlight
ABSTRACT:
SUBMITTER: Gong P
PROVIDER: S-EPMC8277811 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Computational methods have been widely used for the prediction of protein subcellular localization. However, these predictions are rarely validated experimentally and as a result remain questionable. Therefore, experimental validation of the predicted localizations is needed to assess the accuracy of predictions so that such methods can be confidently used to annotate the proteins of unknown localization. Previously, we published a method called ngLOC that predicts the localization of proteins targeted to ten different subcellular organelles. In this short report, we describe the accuracy of these predictions using experimental validations.We have experimentally validated the predicted subcellular localizations of 114 human proteins corresponding to nine different organelles in normal breast and breast cancer cell lines using live cell imaging/confocal microscopy. Target genes were cloned into expression vectors as GFP fusions and cotransfected with RFP-tagged organelle-specific gene marker into normal breast epithelial and breast cancer cell lines. Subcellular localization of each target protein is confirmed by colocalization with a co-expressed organelle-specific protein marker. Our results showed that about 82.5% of the predicted subcellular localizations coincided with the experimentally validated localizations. The highest agreement was found in the endoplasmic reticulum proteins, while the cytoplasmic location showed the least concordance. With the exclusion of cytoplasmic location, the average prediction accuracy increased to 90.4%. In addition, there was no difference observed in the protein subcellular localization between normal and cancer breast cell lines.The experimentally validated accuracy of ngLOC method with (82.5%) or without cytoplasmic location (90.4%) nears the prediction accuracy of 89%. These results demonstrate that the ngLOC method can be very useful for large-scale annotation of the unknown subcellular localization of proteins.
| S-EPMC4301851 | biostudies-literature
Project description:BackgroundSubcellular localization information is one of the key features to protein function research. Locating to a specific subcellular compartment is essential for a protein to function efficiently. Proteins which have multiple localizations will provide more clues. This kind of proteins may take a high proportion, even more than 35%.DescriptionWe have developed a database of proteins with multiple subcellular localizations, designated DBMLoc. The initial release contains 10470 multiple subcellular localization-annotated entries. Annotations are collected from primary protein databases, specific subcellular localization databases and literature texts. All the protein entries are cross-referenced to GO annotations and SwissProt. Protein-protein interactions are also annotated. They are classified into 12 large subcellular localization categories based on GO hierarchical architecture and original annotations. Download, search and sequence BLAST tools are also available on the website.ConclusionDBMLoc is a protein database which collects proteins with more than one subcellular localization annotation. It is freely accessed at http://www.bioinfo.tsinghua.edu.cn/DBMLoc/index.htm.
| S-EPMC2292141 | biostudies-literature
Project description:BackgroundMyosins are actin-activated ATPases that use energy to generate force and move along actin filaments, dragging with their tails different cargos. Plant myosins belong to the group of unconventional myosins and Arabidopsis myosin VIII gene family contains four members: ATM1, ATM2, myosin VIIIA and myosin VIIIB.ResultsIn transgenic plants expressing GFP fusions with ATM1 (IQ-tail truncation, lacking the head domain), fluorescence was differentially distributed: while in epidermis cells at the root cap GFP-ATM1 equally distributed all over the cell, in epidermal cells right above this region it accumulated in dots. Further up, in cells of the elongation zone, GFP-ATM1 was preferentially positioned at the sides of transversal cell walls. Interestingly, the punctate pattern was insensitive to brefeldin A (BFA) while in some cells closer to the root cap, ATM1 was found in BFA bodies. With the use of different markers and transient expression in Nicotiana benthamiana leaves, it was found that myosin VIII co-localized to the plasmodesmata and ER, colocalized with internalized FM4-64, and partially overlapped with the endosomal markers ARA6, and rarely with ARA7 and FYVE. Motility of ARA6 labeled organelles was inhibited whenever associated with truncated ATM1 but motility of FYVE labeled organelles was inhibited only when associated with large excess of ATM1. Furthermore, GFP-ATM1 and RFP-ATM2 (IQ-tail domain) co-localized to the same spots on the plasma membrane, indicating a specific composition at these sites for myosin binding.ConclusionTaken together, our data suggest that myosin VIII functions differently in different root cells and can be involved in different steps of endocytosis, BFA-sensitive and insensitive pathways, ER tethering and plasmodesmatal activity.
| S-EPMC2275265 | biostudies-literature
Project description:Given a query list of genes or proteins, CellWhere produces an interactive graphical display that mimics the structure of a cell, showing the local interaction network organized into subcellular locations. This user-friendly tool helps in the formulation of mechanistic hypotheses by enabling the experimental biologist to explore simultaneously two elements of functional context: (i) protein subcellular localization and (ii) protein-protein interactions or gene functional associations. Subcellular localization terms are obtained from public sources (the Gene Ontology and UniProt-together containing several thousand such terms) then mapped onto a smaller number of CellWhere localizations. These localizations include all major cell compartments, but the user may modify the mapping as desired. Protein-protein interaction listings, and their associated evidence strength scores, are obtained from the Mentha interactome server, or power-users may upload a pre-made network produced using some other interactomics tool. The Cytoscape.js JavaScript library is used in producing the graphical display. Importantly, for a protein that has been observed at multiple subcellular locations, users may prioritize the visual display of locations that are of special relevance to their research domain. CellWhere is at http://cellwhere-myology.rhcloud.com.
| S-EPMC4489307 | biostudies-literature
Project description:The MHC class I gene family of rhesus macaques is characterised by considerable gene duplications. While a HLA-C-orthologous gene is absent, the Mamu-A and in particular the Mamu-B genes have expanded, giving rise to plastic haplotypes with differential gene content. Although some of the rhesus macaque MHC class I genes are known to be associated with susceptibility/resistance to infectious diseases, the functional significance of duplicated Mamu-A and Mamu-B genes and the expression pattern of their encoded proteins are largely unknown. Here, we present data of the subcellular localization of AcGFP-tagged Mamu-A and Mamu-B molecules. We found strong cell surface and low intracellular expression for Mamu-A1, Mamu-A2 and Mamu-A3-encoded molecules as well as for Mamu-B*01704, Mamu-B*02101, Mamu-B*04801, Mamu-B*06002 and Mamu-B*13401. In contrast, weak cell surface and strong intracellular expression was seen for Mamu-A4*1403, Mamu-B*01202, Mamu-B*02804, Mamu-B*03002, Mamu-B*05704, Mamu-I*010201 and Mamu-I*0121. The different expression patterns were assigned to the antigen-binding alpha1 and alpha2 domains, suggesting failure of peptide binding is responsible for retaining 'intracellular' Mamu class I molecules in the endoplasmic reticulum. These findings indicate a diverse functional role of the duplicated rhesus macaque MHC class I genes.
| S-EPMC2827799 | biostudies-literature
Project description:The begomoviruses (BGVs) are plant pathogens that evolved in the Old World during the Cretaceous and arrived to the New World (NW) in the Cenozoic era. A subgroup of NW BGVs, the "Squash leaf curl virus (SLCV) lineage" (S-Lin), includes viruses with unique characteristics. To get clues on the evolutionary origin of this lineage, a search for divergent members was undertaken. Four novel BGVs were characterized, including one that is basal to the group. Comparative analyses led to discover a ~670 bp genome module that is nearly exclusive of this lineage, encompassing the replication origin, the AC4 gene, and 480 bp of the Rep gene. A similar DNA module was found in two curtoviruses, hence suggesting that the S-Lin ancestor acquired its distinctive genomic segment by recombination with a curtovirus. This hypothesis was definitely disproved by an in-depth sequence analysis. The search for homologs of S-Lin Rep uncover the common origin of Rep proteins encoded by diverse Geminiviridae genera and viral "fossils" integrated at plant genomes. In contrast, no homolog of S-Lin Rep was found in public databases. Consequently, it was concluded that the SLCV clade ancestor evolved by a recombination event between a primitive NW BGV and a virus from a hitherto unknown lineage.
| S-EPMC6669703 | biostudies-literature
Project description:Several pathogenic bacteria utilize type III secretion systems (TTSS) to deliver into host cells bacterial virulence proteins with the capacity to modulate a variety of cellular pathways. Once delivered into host cells, the accurate targeting of bacterial effectors to specific locations is critical for their proper function. However, little is known about the mechanisms these virulence effectors use to reach their subcellular destination. Here we show that the Salmonella TTSS effector proteins SspH2 and SseI are localized to the plasma membrane of host cells, a process dependent on S-palmitoylation of a conserved cysteine residue within their N-terminal domains. We also show that effector protein lipidation is mediated by a specific subset of host-cell palmitoyltransferases and that lipidation is critical for effector function. This study describes a remarkable mechanism by which a pathogen exploits host-cell machinery to properly target its virulence factors.
| S-EPMC4326042 | biostudies-literature
Project description:The druggable subset of the human genome, termed the "druggable genome," provides the pharmaceutical industry with a unique opportunity for the advancement of new therapeutic interventions for a multitude of diseases and disorders. To date, there is no systematic assessment of the evolutionary history and nature of the defined druggable proteins derived from the contemporary druggable genome (i.e., proteins that bind or are predicted to bind with high affinity to a biologic). An understanding of drug-protein target interactions in specific cellular compartments is crucial for the optimal therapeutic delivery of pharmaceutical agents, as well as for preclinical drug trials in model animals. This study applied the concept of pharmacophylogenomics, the study of genes, evolution, and drug targets, to conduct an evolutionary survey of drug targets with respect to their subcellular localizations. Using multiple models and modes of druggable genome comparison, the results concordantly indicated that orthologous drug targets with a nuclear localization in the human, macaque, mouse, and rat showed a higher trend for evolutionary conservation compared with drug targets in the cell membrane and the extracellular compartment. As such, this study provides important information regarding druggable protein targets and the druggable genome at the pharmacophylogenomics level.
| S-EPMC3730344 | biostudies-literature
Project description:Fatty acids are important biological components, yet the metabolism of fatty acids in microalgae is not clearly understood. Previous studies found that Chlamydomonas reinhardtii, the model microalga, incorporates exogenously added fatty acids but metabolizes them differently from animals and yeast. Furthermore, a recent metabolic flux analysis found that the majority of lipid turnover in C. reinhardtii is the recycling of acyl chains from and to membranes, rather than β -oxidation. This indicates that for the alga, the maintenance of existing acyl chains may be more valuable than their breakdown for energy. To gain cell-biological knowledge of fatty acid metabolism in C. reinhardtii, we conducted microscopy analysis with fluorescent probes. First, we found that CAT1 (catalase isoform 1) is in the peroxisomes while CAT2 (catalase isoform 2) is localized in the endoplasmic reticulum, indicating the alga is capable of detoxifying hydrogen peroxide that would be produced during β-oxidation in the peroxisomes. Second, we compared the localization of exogenously added FL-C16 (fluorescently labelled palmitic acid) with fluorescently marked endosomes, mitochondria, peroxisomes, lysosomes, and lipid droplets. We found that exogenously added FL-C16 are incorporated and compartmentalized via a non-endocytic route within 10 min. However, the fluorescence signals from FL-C16 did not colocalize with any marked organelles, including peroxisomes. During triacylglycerol accumulation, the fluorescence signals from FL-C16 were localized in lipid droplets. These results support the idea that membrane turnover is favored over β-oxidation in C. reinhardtii. The knowledge gained in these analyses would aid further studies of the fatty acid metabolism.
| S-EPMC8391285 | biostudies-literature
Project description:The MHC class I gene family of rhesus macaques is characterised by considerable gene duplications. While a HLA-C-orthologous gene is absent, the Mamu-A and in particular the Mamu-B genes have expanded, giving rise to plastic haplotypes with differential gene content. Although some of the rhesus macaque MHC class I genes are known to be associated with susceptibility/resistance to infectious diseases, the functional significance of duplicated Mamu-A and Mamu-B genes and the expression pattern of their encoded proteins are largely unknown. Here, we present data of the subcellular localization of AcGFP-tagged Mamu-A and Mamu-B molecules. We found strong cell surface and low intracellular expression for Mamu-A1, Mamu-A2 and Mamu-A3-encoded molecules as well as for Mamu-B*01704, Mamu-B*02101, Mamu-B*04801, Mamu-B*06002 and Mamu-B*13401. In contrast, weak cell surface and strong intracellular expression was seen for Mamu-A4*1403, Mamu-B*01202, Mamu-B*02804, Mamu-B*03002, Mamu-B*05704, Mamu-I*010201 and Mamu-I*0121. The different expression patterns were assigned to the antigen-binding alpha1 and alpha2 domains, suggesting failure of peptide binding is responsible for retaining 'intracellular' Mamu class I molecules in the endoplasmic reticulum. These findings indicate a diverse functional role of the duplicated rhesus macaque MHC class I genes.
| S-EPMC3128699 | biostudies-literature