Alternative splicing controls Leucine-rich repeat domain modularity in NOD-like receptors
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA481458 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7529420_1.fastq.gz | Fastqsanger.gz | |||
| SRR7529420_2.fastq.gz | Fastqsanger.gz | |||
| SRR7529421_1.fastq.gz | Fastqsanger.gz | |||
| SRR7529421_2.fastq.gz | Fastqsanger.gz | |||
| SRR7529422_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Somatic recombination of LRR sequences evolved to create diversity in jawless vertebrate adaptive immunity, yet the role repetitive LRR-encoding exons in humans remains unknown. We performed this RNA Seq study to understand how alternative splicing of NOD-like receptors (NLRs) at the locus encoding a LRR domain can regulate NLRs function, with a focus on NLRP3.
2019-06-09 | GSE117206 | GEO
Project description:Numerous leucine-rich repeat kinase 2 mutations identified throughout the protein are associated with Parkinson disease, however the activating G2019S kinase domain mutation is currently regarded as the most common cause of familial and sporadic forms of this disorder. Despite studies demonstrating the prominent role that its kinase activity plays in the pathobiology of leucine-rich repeat kinase 2, few substrates have been identified and only a subset of these have been linked to disease. Therefore, we utilized protein microarrays to screen over 9,000 human proteins in an unbiased radiometric assay for potential targets of the kinase.
2012-07-14 | GSE30496 | GEO
Project description:Numerous leucine-rich repeat kinase 2 mutations identified throughout the protein are associated with Parkinson disease, however the activating G2019S kinase domain mutation is currently regarded as the most common cause of familial and sporadic forms of this disorder. Despite studies demonstrating the prominent role that its kinase activity plays in the pathobiology of leucine-rich repeat kinase 2, few substrates have been identified and only a subset of these have been linked to disease. Therefore, we utilized protein microarrays to screen over 9,000 human proteins in an unbiased radiometric assay for potential targets of the kinase. ProtoArrayM-bM-^DM-" Human Protein Microarrays v5.0 (Invitrogen, Carlsbad, CA, USA) were used following the manufactureM-bM-^@M-^Ys protocol (ProtoArray Kinase Substrate Identification Kit). Briefly, slides were equilibrated at 4C for 15 min before blocking in 1% BSA in PBS for 1 h at 4oC with gentle shaking. Recombinant G2019S or D1994A glutathione-S-transferase (GST)-LRRK2 (970-2527) (Invitrogen) was diluted to 50nM in 20mM Tris (pH 7.5), 10mM MgCl2, 1mM EGTA, 1mM Na3VO4, 5mM beta-glycerophosphate, 2mM DTT, 0.02% polysorbate 20, and 10 mCi /mL of [gamma- 33P]ATP (33 nM final concentration) in a total volume of 120uL. Slides were overlayed with buffer alone, or buffer containing G2019S or D1994A LRRK2, then covered with a coverslip and placed in a 50 mL conical tube for 1 h at 30oC. Afterwards, slides were washed with 0.5% SDS buffer and water followed by centrifugation. Dried slides were exposed to a PhosphorImager plate (Amersham Biosciences, Piscataway, NJ, USA), and scanned on a Storm 840 (Molecular Dynamics, Inc., Sunnyvale, CA, USA) at 50 microns.
2012-07-13 | E-GEOD-30496 | biostudies-arrayexpress
Project description:The NOD-like receptors (NLRs) and Toll-like receptors (TLRs) are pattern recognition receptors that are involved in the innate, pathogen pattern recognition system. The TLR and NLR receptors contain leucine-rich repeats (LRRs) that are responsible for ligand interactions. In LRRs short β-strands stack parallel and then the LRRs form a super helical arrangement of repeating structural units (called a coil of solenoids). The structures of the LRR domains of NLRC4, NLRP1, and NLRX1 in NLRs and of TLR1-5, TLR6, TLR8, TLR9 in TLRs have been determined. Here we report nine geometrical parameters that characterize the LRR domains; these include four helical parameters from HELFIT analysis. These nine parameters characterize well the LRR structures in NLRs and TLRs; the LRRs of NLR adopts a right-handed helix. In contrast, the TLR LRRs adopt either a left-handed helix or are nearly flat; RP105 and CD14 also adopt a left-handed helix. This geometrical analysis subdivides TLRs into four groups consisting of TLR3/TLR8/TLR9, TLR1/TLR2/TRR6, TLR4, and TLR5; these correspond to the phylogenetic tree based on amino acid sequences. In the TLRs an ascending lateral surface that consists of loops connecting the β-strand at the C-terminal side is involved in protein, protein/ligand interactions, but not the descending lateral surface on the opposite side.
| S-EPMC4598782 | biostudies-literature
Project description:BackgroundThe vast number of precise intercellular connections within vertebrate nervous systems is only partly explained by the comparatively few known extracellular guidance cues. Large families of neural orphan receptor proteins have been identified and are likely to contribute to these recognition processes but due to the technical difficulty in identifying novel extracellular interactions of membrane-embedded proteins, their ligands remain unknown.ResultsTo identify novel neural recognition signals, we performed a large systematic protein interaction screen using an assay capable of detecting low affinity extracellular protein interactions between the ectodomains of 150 zebrafish receptor proteins containing leucine-rich-repeat and/or immunoglobulin superfamily domains. We screened 7,592 interactions to construct a network of 34 cell surface receptor-ligand pairs that included orphan receptor subfamilies such as the Lrrtms, Lrrns and Elfns but also novel ligands for known receptors such as Robos and Unc5b. A quantitative biochemical analysis of a subnetwork involving the Unc5b and three Flrt receptors revealed a surprising quantitative variation in receptor binding strengths. Paired spatiotemporal gene expression patterns revealed dynamic neural receptor recognition maps within the developing nervous system, providing biological support for the network and revealing likely functions.ConclusionsThis integrated interaction and expression network provides a rich source of novel neural recognition pathways and highlights the importance of quantitative systematic extracellular protein interaction screens to mechanistically explain neural wiring patterns.
| S-EPMC2768988 | biostudies-literature
Project description:Oryza sativa (rice) plays an essential food security role for more than half of the world's population. Obtaining crops with high levels of disease resistance is a major challenge for breeders, especially today, given the urgent need for agriculture to be more sustainable. Plant resistance genes are mainly encoded by three large leucine-rich repeat (LRR)-containing receptor (LRR-CR) families: the LRR-receptor-like kinase (LRR-RLK), LRR-receptor-like protein (LRR-RLP) and nucleotide-binding LRR receptor (NLR). Using lrrprofiler, a pipeline that we developed to annotate and classify these proteins, we compared three publicly available annotations of the rice Nipponbare reference genome. The extended discrepancies that we observed for LRR-CR gene models led us to perform an in-depth manual curation of their annotations while paying special attention to nonsense mutations. We then transferred this manually curated annotation to Kitaake, a cultivar that is closely related to Nipponbare, using an optimized strategy. Here, we discuss the breakthrough achieved by manual curation when comparing genomes and, in addition to 'functional' and 'structural' annotations, we propose that the community adopts this approach, which we call 'comprehensive' annotation. The resulting data are crucial for further studies on the natural variability and evolution of LRR-CR genes in order to promote their use in breeding future resilient varieties.
| S-EPMC9292849 | biostudies-literature
Project description:Pseudomonas phaseolicola preferentially modulates genes encoding leucine rich repeat and malectin domains in the bean landrace G2333
| PRJNA725912 | ENA
Project description:Previous studies have shown that non-coding genetic variation in the 5’ region of the leucine-rich repeat kinase 2 (LRRK2) gene contributes to Parkinson's disease risk and influences LRRK2 expression, with the risk allele associated with increased expression of LRRK2. To interrogate the biological basis of this expression quantitative trait locus (eQTL), we used single nuclei RNA sequencing of human frontal cortex from donors with known LRRK2 risk genotypes to show that the eQTL propagates via microglia, despite robust expression of LRRK2 in other cell types. Second, we found that chromatin in the 5’ region of LRRK2 is differentially accessible in microglia compared to other brain cell types using single nuclei ATAC sequencing. We confirmed these effects in a microglia cell model derived from human induced pluripotent stem cells (iPSCs) by generating single cell RNA sequencing and bulk ATAC sequencing datasets. Our results demonstrate that gene expression as a quantitative trait may influence specific cell populations, and that non-coding genetic variants that are associated with other diseases may propagate through restricted cell types.
2021-01-29 | GSE163323 | GEO
Project description:Missense mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene result in late-onset Parkinson’s disease (PD). The incomplete penetrance of LRRK2 mutations in humans and LRRK2 murine models of PD suggests that the disease may result from a complex interplay of genetic predispositions and persistent exogenous insults. To examine molecular pathways that might be affected by mutant LRRK2 in peripheral leukocytes, we performed mass spectrometry analysis (tandem mass tagging, TMT) on peripheral blood mononuclear cells obtained from intact and acute LPS-challenged WT and R1441G mutant mice.
2018-05-03 | PXD006289 | Pride
Project description:Missense mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene result in late-onset Parkinson’s disease (PD). The incomplete penetrance of LRRK2 mutations in humans and LRRK2 murine models of PD suggests that the disease may result from a complex interplay of genetic predispositions and persistent exogenous insults. To achieve a detailed characterization of the altered neuroinflammatory reaction in the brain of mutant LRRK2 mice, we performed mass spectrometry analysis (tandem mass tagging, TMT) of brain tissue obtained from intact and acute LPS-challenged WT and R1441G mutant mice.
2018-05-03 | PXD006290 | Pride