Abstract:
:Retinoic acid-inducible gene I (RIG-I) is an important pattern recognition receptor that detects viral RNA and triggers the production of type-I interferons through the downstream adaptor MAVS (also called IPS-1, CARDIF, or VISA). A series of structural studies have elaborated some of the mechanisms of dsRNA recognition and activation of RIG-I. Recent studies have proposed that K63-linked ubiquitination of, or unanchored K63-linked polyubiquitin binding to RIG-I positively regulates MAVS-mediated antiviral signaling. Conversely phosphorylation of RIG-I appears to play an inhibitory role in controlling RIG-I antiviral signal transduction. Here we performed a combined structural and biochemical study to further define the regulatory features of RIG-I signaling. ATP and dsRNA binding triggered dimerization of RIG-I with conformational rearrangements of the tandem CARD domains. Full length RIG-I appeared to form a complex with dsRNA in a 2:2 molar ratio. Compared with the previously reported crystal structures of RIG-I in inactive state, our electron microscopic structure of full length RIG-I in complex with blunt-ended dsRNA, for the first time, revealed an exposed active conformation of the CARD domains. Moreover, we found that purified recombinant RIG-I proteins could bind to the CARD domain of MAVS independently of dsRNA, while S8E and T170E phosphorylation-mimicking mutants of RIG-I were defective in binding E3 ligase TRIM25, unanchored K63-linked polyubiquitin, and MAVS regardless of dsRNA. These findings suggested that phosphorylation of RIG inhibited downstream signaling by impairing RIG-I binding with polyubiquitin and its interaction with MAVS.
journal_name
Protein Celljournal_title
Protein & cellauthors
Feng M,Ding Z,Xu L,Kong L,Wang W,Jiao S,Shi Z,Greene MI,Cong Y,Zhou Zdoi
10.1007/s13238-012-2088-4subject
Has Abstractpub_date
2013-02-01 00:00:00pages
142-54issue
2eissn
1674-800Xissn
1674-8018journal_volume
4pub_type
杂志文章相关文献
Protein & Cell文献大全abstract::Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing β-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes)...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-012-2055-0
更新日期:2012-10-01 00:00:00
abstract::Flea-borne transmission is a recent evolutionary adaptation that distinguishes the deadly Yersinia pestis from its progenitor Y. Pseudotuberculosis, a mild pathogen transmitted via the food-borne route. Y. Pestis synthesizes biofilms in the flea gut, which is important for fleaborne transmission. Yersinia biofilms are...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-011-1024-3
更新日期:2011-03-01 00:00:00
abstract::Human embryonic stem cells (hESCs) depend on glycolysis for energy and substrates for biosynthesis. To understand the mechanisms governing the metabolism of hESCs, we investigated the transcriptional regulation of glucose transporter 1 (GLUT1, SLC2A1), a key glycolytic gene to maintain pluripotency. By combining the g...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-019-0637-9
更新日期:2019-09-01 00:00:00
abstract::The fungus Trichophyton schoenleinii (T. schoenleinii) is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa. Human innate immune system plays an important role in combating with various pathogens including fungi. The inflammasome is one of the most critical ar...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-013-2127-9
更新日期:2013-07-01 00:00:00
abstract::Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The majority of approved recombinant monoclonal antibody therapies are of the human IgG1 subclass, which c...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-017-0473-8
更新日期:2018-01-01 00:00:00
abstract::Hannum and colleagues performed DNA methylation sequencing to examine the relationship between DNA methylome and aging rate. Notably, they succeeded in building a quantitative and reproducible model based on the epigenetic bio-markers to predict aging rate with high accuracy. This progress enlightens us in many aspect...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-013-3913-0
更新日期:2013-10-01 00:00:00
abstract::Progranulin (PGRN) is a growth factor implicated in various pathophysiological processes, including wound healing, inflammation, tumorigenesis, and neurodegeneration. It was previously reported that PGRN binds to tumor necrosis factor receptors (TNFR) and has therapeutic effects in inflammatory arthritis (Tang et. al,...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-015-0213-x
更新日期:2015-11-01 00:00:00
abstract::Siva-1, as a p53-inducible gene, has been shown to induce extensive apoptosis in a number of different cell lines. Recent evidence suggests that Siva-1 functions as a part of the auto-regulatory feedback loop that restrains p53 through facilitating Mdm2-mediated p53 degradation. Also, Siva-1 plays an important role in...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-012-2018-5
更新日期:2012-02-01 00:00:00
abstract::In the original publication the PDB numbers were not cited. ...
journal_title:Protein & cell
pub_type: 已发布勘误
doi:10.1007/s13238-019-0619-y
更新日期:2019-07-01 00:00:00
abstract::Macroautophagy is an evolutionarily conserved intracellular degradation system used by life ranging from yeasts to mammals. The core autophagic machinery is composed of ATG (autophagy-related) protein constituents. One particular member of the ATG protein family, Atg7, has been the focus of recent research. Atg7 acts ...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-015-0195-8
更新日期:2015-10-01 00:00:00
abstract::The human Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor 1-like (Efl1), to promote the release of eukaryotic initiation factor 6 (eIF6...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-015-0242-5
更新日期:2016-03-01 00:00:00
abstract::CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle, inflammation, and tumorigenesis and is highly expressed in many types of tumors. CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibi...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-011-1089-z
更新日期:2011-09-01 00:00:00
abstract::A chimeric protein called Wallerian degeneration slow (Wld(S)) was first discovered in a spontaneous mutant strain of mice that exhibited delayed Wallerian degeneration. This provides a useful tool in elucidating the mechanisms of axon degeneration. Over-expression of Wld(S) attenuates the axon degeneration that is as...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-010-0021-2
更新日期:2010-03-01 00:00:00
abstract::ATP-sensitive potassium channels (KATP) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic KATP channels control insulin release and regulate metabolism at the whole body level. They are implicated in many metabolic disorders and diseases and are therefore impo...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-018-0530-y
更新日期:2018-06-01 00:00:00
abstract::Complement proteins in blood recognize charged particles. The anionic phospholipid (aPL) cardiolipin binds both complement proteins C1q and factor H. C1q is an activator of the complement classical pathway, while factor H is an inhibitor of the alternative pathway. To examine opposing effects of C1q and factor H on co...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-010-0125-8
更新日期:2010-11-01 00:00:00
abstract::Polycomb Group Proteins (PcG) are a family of epigenetic regulators responsible for the repression of an array of genes important in development and cell fate specification. PcG proteins complex to form two types of epigenetic regulators: Polycomb Repressive Complex 1 and 2 (PRC1 and PRC2). Although the mechanisms reg...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-010-0142-7
更新日期:2010-12-01 00:00:00
abstract::Human pluripotent stem cells (hPSCs) are an important system to study early human development, model human diseases, and develop cell replacement therapies. However, genetic manipulation of hPSCs is challenging and a method to simultaneously activate multiple genomic sites in a controllable manner is sorely needed. He...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-016-0360-8
更新日期:2017-05-01 00:00:00
abstract::Histone deacetylase 6 (HDAC6), a predominantly cytoplasmic protein deacetylase, participates in a wide range of cellular processes through its deacetylase activity. However, the diverse functions of HDAC6 cannot be fully elucidated with its known substrates. In an attempt to explore the substrate diversity of HDAC6, w...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-014-0102-8
更新日期:2015-01-01 00:00:00
abstract::FcγRIIB, the only inhibitory IgG Fc receptor, functions to suppress the hyper-activation of immune cells. Numerous studies have illustrated its inhibitory function through the ITIM motif in the cytoplasmic tail of FcγRIIB. However, later studies revealed that in addition to the ITIM, the transmembrane (TM) domain of F...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-018-0509-8
更新日期:2018-12-01 00:00:00
abstract::Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome p...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-020-00720-y
更新日期:2020-06-01 00:00:00
abstract::Thymic epithelial cells (TECs) are one of the most important components in thymic microenvironment supporting thymocyte development and maturation. TECs, composed of cortical and medullary TECs, are derived from a common bipotent progenitor, mediating thymocyte positive and negative selections. Multiple levels of sign...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-013-3014-0
更新日期:2013-05-01 00:00:00
abstract::Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-019-0608-1
更新日期:2019-04-01 00:00:00
abstract::With the smooth move towards the coming expected clinical reports of anticancer pharmaceutical molecules targeting telomeres and telomerase, and also with the exciting success in the extension of lifespan by regulating telomerase activity without increased onset of oncogenesis in laboratory mouse models (Garcia-Cao et...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-013-3002-4
更新日期:2013-08-01 00:00:00
abstract::Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC popu...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-015-0140-x
更新日期:2015-04-01 00:00:00
abstract::Leukocyte immunoglobulin-like receptors (LILRs), also called CD85s, ILTs, or LIRs, are important mediators of immune activation and tolerance that contain tandem immunoglobulin (Ig)-like folds. There are 11 (in addition to two pseudogenes) LILRs in total, two with two Ig-like domains (D1D2) and the remaining nine with...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-013-3908-x
更新日期:2013-10-01 00:00:00
abstract::Sometimes crystals cannot diffract X-rays beyond 3.0 Å resolution due to the intrinsic flexibility associated with the protein. Low resolution diffraction data not only pose a challenge to structure determination, but also hamper interpretation of mechanistic details. Crystals of a 25.6 kDa non-Pfam, hypothetical prot...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-010-0045-7
更新日期:2010-05-01 00:00:00
abstract::Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-020-00753-3
更新日期:2020-07-14 00:00:00
abstract::Treatment of latent tuberculosis infection remains an important goal of global TB eradication. To this end, targets that are essential for intracellular survival of Mycobacterium tuberculosis are particularly attractive. Arylamine N-acetyltransferase (NAT) represents such a target as it is, along with the enzymes enco...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-010-0037-7
更新日期:2010-04-01 00:00:00
abstract::We recently found that growth factor receptor-bound (Grb) protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit (CNGA1). Grb14 promotes the CNG channel closure through its Ras-associating (RA) domain. In the current study we show that this RA domain-media...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-011-1115-1
更新日期:2011-11-01 00:00:00
abstract::Human monocyte is an important cell type which is involved in various complex human diseases. To better understand the biology of human monocytes and facilitate further studies, we developed the first comprehensive proteome knowledge base specifically for human monocytes by integrating both in vivo and in vitro datase...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-016-0342-x
更新日期:2017-02-01 00:00:00