Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Crystal and solution structure of the human RIG-I SF2 domain.

ABSTRACT: RIG-I is a pathogen-recognition receptor that recognizes viral 5'-triphosphates carrying double-stranded RNA. Upon binding to these microbe-associated molecular patterns (MAMPs), RIG-I forms oligomers and promotes downstream processes that result in type I interferon production and induction of an antiviral state. Here, the crystal structure of the human RIG-I superfamily 2 ATPase domain crystallized in an unusually elongated and open conformation is reported. The elongated structure is probably induced in part by crystal packing, but nevertheless indicates that the domain is intrinsically very flexible. This flexibility might allow substantial structural changes upon substrate binding and oligomerization.

SUBMITTER: Deimling T

PROVIDER: S-EPMC4118797 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Crystal and solution structure of the human RIG-I SF2 domain.

Deimling Tobias T Cui Sheng S Lammens Katja K Hopfner Karl-Peter KP Witte Gregor G

Acta crystallographica. Section F, Structural biology communications 20140723 Pt 8

RIG-I is a pathogen-recognition receptor that recognizes viral 5'-triphosphates carrying double-stranded RNA. Upon binding to these microbe-associated molecular patterns (MAMPs), RIG-I forms oligomers and promotes downstream processes that result in type I interferon production and induction of an antiviral state. Here, the crystal structure of the human RIG-I superfamily 2 ATPase domain crystallized in an unusually elongated and open conformation is reported. The elongated structure is probably ...[more]

PMID: 25084375

Similar Datasets

Crystal Structure of Human Nocturnin Catalytic Domain.

Project description:Nocturnin (NOCT) helps the circadian clock to adjust metabolism according to day and night activity. NOCT is upregulated in early evening and it has been proposed that NOCT serves as a deadenylase for metabolic enzyme mRNAs. We present a 2.7-Å crystal structure of the catalytic domain of human NOCT. Our structure shows that NOCT has a close overall similarity to CCR4 deadenylase family members, PDE12 and CNOT6L, and to a DNA repair enzyme TDP2. All the key catalytic residues present in PDE12, CNOT6L and TDP2 are conserved in NOCT and have the same conformations. However, we observe substantial differences in the surface properties of NOCT, an unexpectedly narrow active site pocket, and conserved structural elements in the vicinity of the catalytic center, which are unique to NOCT and absent in the deadenylases PDE12/CNOT6L. Moreover, we show that in contrast to human PDE12 and CNOT6L, NOCT is completely inactive against poly-A RNA. Our work thus reveals the structure of an intriguing circadian protein and suggests that NOCT has considerable differences from the related deadenylases, which may point to a unique cellular function of this enzyme.

| S-EPMC6214945 | biostudies-literature

Crystal structure of human Ankyrin G death domain.

Project description:Ankyrins (Ank) are a ubiquitously expressed family of multifunctional membrane adapter proteins. Ankyrin G (AnkG) is critical for assembling and maintenance of the axon initial segment. Here we present the 2.1 Å crystal structure of human AnkG death domain (hAnkG-DD). The core death domain is composed of six ?-helices and three 3??-helices. It forms a hydrophobic pocket on the surface of the molecule. The C-terminal tail of the hAnkG-DD curves back to have the aromatic ring of a phenylalanine residue, Phe100 insert into this pocket, which anchors the flexible tail onto the core domain. Related DDs were selected for structure comparison. The major variations are at the C-terminal region, including the ?6 and the long C-terminal extension. The results of size exclusion chromatography and analytical ultracentrifugation suggest that hAnkG-DD exists as monomer in solution. Our work should help for the future investigation of the structure-function of AnkG.

| S-EPMC4258306 | biostudies-literature

Crystal structure of the human spastin AAA domain.

Project description:Hereditary spastic paraplegia (HSP) is a motor neuron disease caused by a progressive degeneration of the motor axons of the corticospinal tract. Point mutations or exon deletions in the microtubule-severing ATPase, spastin, are responsible for approximately 40% of cases of autosomal dominant HSP. Here, we report the 3.3 Å X-ray crystal structure of a hydrolysis-deficient mutant (E442Q) of the human spastin protein AAA domain. This structure is analyzed in the context of the existing Drosophila melanogaster spastin AAA domain structure and crystal structures of other closely related proteins in order to build a more unifying framework for understanding the structural features of this group of microtubule-severing ATPases.

| S-EPMC3411929 | biostudies-literature

Crystal structure of RIG-I C-terminal domain bound to blunt-ended double-strand RNA without 5' triphosphate.

Project description:RIG-I recognizes molecular patterns in viral RNA to regulate the induction of type I interferons. The C-terminal domain (CTD) of RIG-I exhibits high affinity for 5' triphosphate (ppp) dsRNA as well as blunt-ended dsRNA. Structures of RIG-I CTD bound to 5'-ppp dsRNA showed that RIG-I recognizes the termini of dsRNA and interacts with the ppp through electrostatic interactions. However, the structural basis for the recognition of non-phosphorylated dsRNA by RIG-I is not fully understood. Here, we show that RIG-I CTD binds blunt-ended dsRNA in a different orientation compared to 5' ppp dsRNA and interacts with both strands of the dsRNA. Overlapping sets of residues are involved in the recognition of blunt-ended dsRNA and 5' ppp dsRNA. Mutations at the RNA-binding surface affect RNA binding and signaling by RIG-I. These results provide the mechanistic basis for how RIG-I recognizes different RNA ligands.

| S-EPMC3045611 | biostudies-literature

Crystal structure of the catalytic domain of human RPTPH.

Project description:Receptor-type protein tyrosine phosphatases (RPTPs) receive extracellular stimuli and transfer them into cells. They regulate cell growth, differentiation and death via specific signals. They have also been implicated in cancer, diabetes and neurological diseases. RPTPH, a member of the type 3 RPTP (R3-PTP) family, is an important regulator of colorectal cancer and hepatic carcinoma. Despite its importance in drug development, the structure of RPTPH has not yet been resolved. Here, the crystal structure of the catalytic domain of RPTPH was determined at 1.56 Å resolution. Despite similarities to other R3-PTPs in its overall structure, RPTPH exhibited differences in its loop regions and side-chain conformations. Compared with other R3-PTPs, RPTPH has unique side chains near its active site that may confer specificity for inhibitor binding. Therefore, detailed information on the structure of RPTPH provides clues for the development of specific inhibitors.

| S-EPMC9254897 | biostudies-literature

Crystal structure of human Acinus RNA recognition motif domain.

Project description:Acinus is an abundant nuclear protein involved in apoptosis and splicing. It has been implicated in inducing apoptotic chromatin condensation and DNA fragmentation during programmed cell death. Acinus undergoes activation by proteolytic cleavage that produces a truncated p17 form that comprises only the RNA recognition motif (RRM) domain. We have determined the crystal structure of the human Acinus RRM domain (AcRRM) at 1.65 Å resolution. It shows a classical four-stranded antiparallel β-sheet fold with two flanking α-helices and an additional, non-classical α-helix at the C-terminus, which harbors the caspase-3 target sequence that is cleaved during Acinus activation. In the structure, the C-terminal α-helix partially occludes the potential ligand binding surface of the β-sheet and hypothetically shields it from non-sequence specific interactions with RNA. Based on the comparison with other RRM-RNA complex structures, it is likely that the C-terminal α-helix changes its conformation with respect to the RRM core in order to enable RNA binding by Acinus.

| S-EPMC6057467 | biostudies-literature

NMR solution structure of the activation domain of human procarboxypeptidase A2.

Project description:The activation domain of human procarboxypeptidase A2, ADA2h, is an 81-residue globular domain released during the proteolytic activation of the proenzyme. The role of this and other similar domains as assistants of the correct folding of the enzyme is not fully understood. The folding pathway of ADA2h was characterized previously, and it was also observed that under certain conditions it may convert into amyloid fibrils in vitro. To gain insight into these processes, a detailed description of its three-dimensional structure in aqueous solution is required so that eventual changes could be properly monitored. A complete assignment of the (1)H and (15)N resonances of ADA2h was performed, and the solution structure, as derived from a set of 1688 nonredundant constraints, is very well defined (pairwise backbone RMSD = 0.67 +/- 0.17 A for residues 10-80). The structure is composed of two antiparallel alpha-helices comprising residues 19-32 and 58-69 packed on the same side of a three-stranded beta-sheet spanning residues 10-15, 50-55, and 73-75. The global fold for the isolated human A2 activation domain is very similar to that of porcine carboxypeptidase B, as well as to the structure of the domain in the crystal of the intact human proenzyme. The observed structural differences relative to the intact human proenzyme are located at the interface between the activation domain and the enzyme and can be related with the activation mechanism. The backbone amide proton exchange behavior of ADA2h was also examined. The global free energy of unfolding obtained from exchange data of the most protected amide protons at pH 7.0 and 298K is 4.9 +/- 0.3 kcal.mole(-1), in good agreement with the values determined by thermal or denaturant unfolding studies.

| S-EPMC2312417 | biostudies-literature

Crystal structure of the human TRPV2 channel ankyrin repeat domain.

Project description:TRPV channels are important polymodal integrators of noxious stimuli mediating thermosensation and nociception. An ankyrin repeat domain (ARD), which is a common protein-protein recognition domain, is conserved in the N-terminal intracellular domain of all TRPV channels and predicted to contain three to four ankyrin repeats. Here we report the first structure from the TRPV channel subfamily, a 1.7 A resolution crystal structure of the human TRPV2 ARD. Our crystal structure reveals a six ankyrin repeat stack with multiple insertions in each repeat generating several unique features compared with a canonical ARD. The surface typically used for ligand recognition, the ankyrin groove, contains extended loops with an exposed hydrophobic patch and a prominent kink resulting from a large rotational shift of the last two repeats. The TRPV2 ARD provides the first structural insight into a domain that coordinates nociceptive sensory transduction and is likely to be a prototype for other TRPV channel ARDs.

| S-EPMC2242602 | biostudies-literature

Crystal structure of the TLDc domain of human NCOA7-AS.

Project description:The TLDc [Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic] domain is associated with oxidation-resistance related functions and is well conserved among eukaryotes. Seven proteins possess a TLDc domain in humans, notably proteins belonging to the oxidation resistance protein (OXR), nuclear receptor coactivator 7 (NCOA7) and TBC1 domain family member 24 (TBC1D24) families. Although the mechanism is unknown, a protective role of TLDc proteins against oxidative stress, notably in the brain, has been demonstrated. Neurobiological disorders caused by mutations in the TLDc domain have also been reported. The human NCOA7 gene encodes several mRNA isoforms; among these, isoform 4, named NCOA7-AS, is up-regulated by type 1 interferon in response to viral infection. NCOA7 and NCOA7-AS both interact with several subunits of the vacuolar proton pump V-ATPase, which leads to increased acidification of the endolysosomal system and consequently impairs infection by viruses that enter their host cells through the endosomal pathway, such as influenza A virus and hepatitis C virus. Similarly to full-length NCOA7, NCOA7-AS possesses a TLDc domain in its C-terminus. Structures of TLDc domains have been reported from zebrafish and fly but not from humans. Here, the expression, purification and crystallization of the TLDc domain from NCOA7 and NCOA7-AS is reported. The crystal structure solved at 1.8 Å resolution is compared with previously solved three-dimensional structures of TLDc domains.

| S-EPMC8329711 | biostudies-literature

Solution structure of the antifreeze-like domain of human sialic acid synthase.

Project description:The structure of the C-terminal antifreeze-like (AFL) domain of human sialic acid synthase was determined by NMR spectroscopy. The structure comprises one alpha- and two single-turn 3(10)-helices and two beta-strands, and is similar to those of the type III antifreeze proteins. Evolutionary trace analyses of the type III antifreeze protein family suggested that the class-specific residues in the human and bacterial AFL domains are important for their substrate binding, while the class-specific residues of the fish antifreeze proteins are gathered on the ice-binding surface.

| S-EPMC2242509 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data