Abstract:
:The unfolded protein response (UPR) adjusts the cell's protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α's ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD's MHC-like groove and induce allosteric changes that lead to its oligomerization. Mutation of a hydrophobic patch at the oligomerization interface decoupled peptide binding to hIRE1α LD from its oligomerization, yet retained peptide-induced allosteric coupling within the domain. Importantly, impairing oligomerization of hIRE1α LD abolished IRE1's activity in living cells. Our results provide evidence for a unifying mechanism of IRE1 activation that relies on unfolded protein binding-induced oligomerization.
journal_name
Elifejournal_title
eLifeauthors
Karagöz GE,Acosta-Alvear D,Nguyen HT,Lee CP,Chu F,Walter Pdoi
10.7554/eLife.30700subject
Has Abstractpub_date
2017-10-03 00:00:00issn
2050-084Xpii
30700journal_volume
6pub_type
杂志文章相关文献
eLife文献大全abstract::Disturbance from whale-watching can cause significant behavioural changes with fitness consequences for targeted whale populations. However, the sensory stimuli triggering these responses are unknown, preventing effective mitigation. Here, we test the hypothesis that vessel noise level is a driver of disturbance, usin...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56760
更新日期:2020-06-16 00:00:00
abstract::Vertebrate embryonic patterning depends on signaling from Nodal, a TGFβ superfamily member. There are three Nodal orthologs in zebrafish; southpaw directs left-right asymmetries, while squint and cyclops function earlier to pattern mesendoderm. TGFβ member Vg1 is implicated in mesoderm formation but the role of the ze...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.28635
更新日期:2017-11-15 00:00:00
abstract::MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgr...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.23813
更新日期:2017-04-19 00:00:00
abstract::Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function. It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.32017
更新日期:2018-03-20 00:00:00
abstract::Methyl-coenzyme M reductase (MCR), found in strictly anaerobic methanogenic and methanotrophic archaea, catalyzes the reversible production and consumption of the potent greenhouse gas methane. The α subunit of MCR (McrA) contains several unusual post-translational modifications, including a rare thioamidation of glyc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.29218
更新日期:2017-09-07 00:00:00
abstract::Recent transcriptional profiling technologies are uncovering previously-undefined cell populations and molecular markers at an unprecedented pace. While single cell RNA (scRNA) sequencing is an attractive approach for unbiased transcriptional profiling of all cell types, a complementary method to isolate and sequence ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.51452
更新日期:2019-12-09 00:00:00
abstract::Convenient, efficient and fast whole-brain delivery of transgenes presents a persistent experimental challenge in neuroscience. Recent advances demonstrate whole-brain gene delivery by retro-orbital injection of virus, but slow and sparse expression and the large injection volumes required make this approach cumbersom...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.53639
更新日期:2020-05-18 00:00:00
abstract::The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34420
更新日期:2018-03-28 00:00:00
abstract::Cells respond to protein misfolding and aggregation in the cytosol by adjusting gene transcription and a number of post-transcriptional processes. In parallel to functional reactions, cellular structure changes as well; however, the mechanisms underlying the early adaptation of cellular compartments to cytosolic prote...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.29388
更新日期:2017-11-01 00:00:00
abstract::Adhesion molecules hold cells together but also couple cell membranes to a contractile actomyosin network, which limits the expansion of cell contacts. Despite their fundamental role in tissue morphogenesis and tissue homeostasis, how adhesion molecules control cell shapes and cell patterns in tissues remains unclear....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.22796
更新日期:2017-05-24 00:00:00
abstract::Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.58593
更新日期:2020-10-22 00:00:00
abstract::Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryonic development. Here we show that genome-wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with r...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.09571
更新日期:2015-11-09 00:00:00
abstract::R-loops are features of chromatin consisting of a strand of DNA hybridized to RNA, as well as the expelled complementary DNA strand. R-loops are enriched at promoters where they have recently been shown to have important roles in modifying gene expression. However, the location of promoter-associated R-loops and the g...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.28306
更新日期:2017-10-26 00:00:00
abstract::Studies of the performance of individuals with dyslexia in perceptual tasks suggest that their implicit inference of sound statistics is impaired. Previously, using two-tone frequency discrimination, we found that the effect of previous trials' frequencies on the judgments of individuals with dyslexia decays faster th...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30018
更新日期:2018-02-28 00:00:00
abstract:Background:Malaria elimination strategies require a thorough understanding of parasite transmission from human to mosquito. A clinical model to induce gametocytes to understand their dynamics and evaluate transmission-blocking interventions (TBI) is currently unavailable. Here, we explore the use of the well-establishe...
journal_title:eLife
pub_type: 杂志文章,随机对照试验
doi:10.7554/eLife.31549
更新日期:2018-02-27 00:00:00
abstract::Skeletal muscle degeneration is a complication arising from a variety of chronic diseases including advanced cancer. Pro-inflammatory cytokine TNF-α plays a pivotal role in mediating cancer-related skeletal muscle degeneration. Here, we show a novel function for retinoblastoma protein (Rb), where Rb causes sarcomeric ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01228
更新日期:2013-12-03 00:00:00
abstract::The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.14620
更新日期:2016-04-14 00:00:00
abstract::Grid cells in the brain respond when an animal occupies a periodic lattice of 'grid fields' during navigation. Grids are organized in modules with different periodicity. We propose that the grid system implements a hierarchical code for space that economizes the number of neurons required to encode location with a giv...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.08362
更新日期:2015-09-03 00:00:00
abstract::The Hippo-YAP pathway is a central regulator of cell contact inhibition, proliferation and death. There are conflicting reports regarding the role of Angiomotin (Amot) in regulating this pathway. While some studies suggest a YAP-inhibitory function other studies indicate Amot is required for YAP activity. Here, we des...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.23966
更新日期:2017-05-03 00:00:00
abstract::TFIID-a complex of TATA-binding protein (TBP) and TBP-associated factors (TAFs)-is a central component of the Pol II promoter recognition apparatus. Recent studies have revealed significant downregulation of TFIID subunits in terminally differentiated myocytes, hepatocytes and adipocytes. Here, we report that TBP prot...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.08536
更新日期:2015-09-22 00:00:00
abstract::A small transparent crustacean called Parhyale hawaiensis has become a powerful model system for the study of limb and appendage regeneration. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.21583
更新日期:2016-10-25 00:00:00
abstract::Proteasome inhibition elicits an evolutionarily conserved response wherein proteasome subunit mRNAs are upregulated, resulting in recovery (i.e., 'bounce-back') of proteasome activity. We previously demonstrated that the transcription factor Nrf1/NFE2L1 mediates this homeostatic response in mammalian cells. We show he...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01856
更新日期:2014-01-01 00:00:00
abstract::The mechanisms underlying axon regeneration in mature neurons are relevant to the understanding of normal nervous system maintenance and for developing therapeutic strategies for injury. Here, we report novel pathways in axon regeneration, identified by extending our previous function-based screen using the C. elegans...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.39756
更新日期:2018-11-21 00:00:00
abstract::Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cel...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.22279
更新日期:2017-02-17 00:00:00
abstract::The representation of position in the mammalian brain is distributed across multiple neural populations. Grid cell modules in the medial entorhinal cortex (MEC) express activity patterns that span a low-dimensional manifold which remains stable across different environments. In contrast, the activity patterns of hippo...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56894
更新日期:2020-08-11 00:00:00
abstract::Nutritional regulation by ants emerges from a distributed process: food is collected by a small fraction of workers, stored within the crops of individuals, and spread via local ant-to-ant interactions. The precise individual-level underpinnings of this collective regulation have remained unclear mainly due to difficu...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.31730
更新日期:2018-03-06 00:00:00
abstract::It is widely argued that personalized instruction based on individual differences in learning styles or genetic predispositions could improve learning outcomes. However, this proposition has resisted clear demonstration in human studies, where it is difficult to control experience and quantify outcomes. Here, we take ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47216
更新日期:2019-09-17 00:00:00
abstract::Drug treatment of 3D cancer spheroids more accurately reflects in vivo therapeutic responses compared to adherent culture studies. In EGFR-mutated lung adenocarcinoma, EGFR-TKIs show enhanced efficacy in spheroid cultures. Simultaneous inhibition of multiple parallel RTKs further enhances EGFR-TKI effectiveness. We sh...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.58204
更新日期:2020-09-08 00:00:00
abstract::Toothed whales use sonar to detect, locate, and track prey. They adjust emitted sound intensity, auditory sensitivity and click rate to target range, and terminate prey pursuits with high-repetition-rate, low-intensity buzzes. However, their narrow acoustic field of view (FOV) is considered stable throughout target ap...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05651
更新日期:2015-03-20 00:00:00
abstract::Vitamin B12 (cobalamin) is the most complex B-type vitamin and is synthetized exclusively in a limited number of prokaryotes. Its biologically active variants contain rare organometallic bonds, which are used by enzymes in a variety of central metabolic pathways such as L-methionine synthesis and ribonucleotide reduct...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.35828
更新日期:2018-05-29 00:00:00