Search results for " nucleotide-binding domain"

showing 8 items of 8 documents

Solution Structure of the R3H Domain from Human Sμbp-2

2003

The R3H domain is a conserved sequence motif, identified in over 100 proteins, that is thought to be involved in polynucleotide-binding, including DNA, RNA and single-stranded DNA. In this work the 3D structure of the R3H domain from human Smubp-2 was determined by NMR spectroscopy. It is the first 3D structure determination of an R3H domain. The fold presents a small motif, consisting of a three-stranded antiparallel beta-sheet and two alpha-helices, which is related to the structures of the YhhP protein and the C-terminal domain of the translational initiation factor IF3. The similarities are non-trivial, as the amino acid identities are below 10%. Three conserved basic residues cluster o…

Models MolecularEGF-like domainMolecular Sequence DataProtein domainProkaryotic Initiation Factor-3Immunoglobulin domainStructure-Activity RelationshipBacterial ProteinsStructural BiologyEVH1 domainHumansAmino Acid SequenceB3 domainNuclear Magnetic Resonance BiomolecularMolecular BiologyChemistryEscherichia coli ProteinsDHR1 domainProtein Structure TertiaryDNA-Binding ProteinsSolutionsCrystallographyCyclic nucleotide-binding domainSequence AlignmentTranscription FactorsBinding domainJournal of Molecular Biology
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Plasticity of the PAS domain and a potential role for signal transduction in the histidine kinase DcuS

2008

The mechanistic understanding of how membrane-embedded sensor kinases recognize signals and regulate kinase activity is currently limited. Here we report structure-function relationships of the multidomain membrane sensor kinase DcuS using solid-state NMR, structural modeling and mutagenesis. Experimental data of an individual cytoplasmic Per-Arnt-Sim (PAS) domain were compared to structural models generated in silico. These studies, together with previous NMR work on the periplasmic PAS domain, enabled structural investigations of a membrane-embedded 40-kDa construct by solid-state NMR, comprising both PAS segments and the membrane domain. Structural alterations are largely limited to prot…

Models MolecularCytoplasmHistidine KinaseMolecular Sequence DataHAMP domainStructural BiologyPAS domainEscherichia coliAmino Acid SequenceKinase activityProtein Structure QuaternaryNuclear Magnetic Resonance BiomolecularMolecular BiologybiologyEscherichia coli ProteinsHistidine kinaseProtein Structure TertiaryCell biologyTransmembrane domainBiochemistryProtein kinase domainCyclic nucleotide-binding domainbiology.proteinGRB2Protein KinasesSignal Transduction
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Human Inducible Hsp70: Structures, Dynamics, and Interdomain Communication from All-Atom Molecular Dynamics Simulations

2015

The 70 kDa human heat shock protein is a major molecular chaperone involved in de novo folding of proteins in vivo and refolding of proteins under stress conditions. Hsp70 is related to several "misfolding diseases" and other major pathologies, such as cancer, and is a target for new therapies. Hsp70 is comprised of two main domains: an N-terminal nucleotide binding domain (NBD) and a C-terminal substrate protein binding domain (SBD). The chaperone function of Hsp70 is based on an allosteric mechanism. Binding of ATP in NBD decreases the affinity of the substrate for SBD, and hydrolysis of ATP is promoted by binding of polypeptide segments in the SBD. No complete structure of human Hsp70 is…

Conformational changebiologySaccharomyces cerevisiaeAllosteric regulationPlasma protein bindingbiology.organism_classificationComputer Science ApplicationsMolecular dynamicsBiochemistryCyclic nucleotide-binding domainATP hydrolysisChaperone (protein)biology.proteinBiophysicsPhysical and Theoretical ChemistryJournal of Chemical Theory and Computation
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The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor

2021

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …

0301 basic medicineBiFC bimolecular fluorescence complementationMST microscale thermophoresisPDIA1 protein disulfide isomerase family A member 1ApoptosisNEUROTROPHIC FACTOR MANFEndoplasmic ReticulumBiochemistryprotein-protein interactionMiceBimolecular fluorescence complementationUPR unfolded protein responseENDOPLASMIC-RETICULUM STRESSMesencephalonNeurotrophic factorsInsulin-Secreting CellsProtein Interaction MappingBINDINGCOMPREHENSIVE RESOURCEATF6unfolded protein response (UPR)PDIA6 protein disulfide isomerase family A member 6PPIs protein-protein interactionsEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsNPTN neuroplastinbiologyChemistryapoptosisunfolded protein responsedopamine neurons3. Good healthCell biologyGDNF glial cell line–derived neurotrophic factorIRE1-ALPHASBD substrate-binding domainendoplasmic reticulum stressMANF mesencephalic astrocyte-derived neurotrophic factorTm tunicamycinneuroprotectionResearch ArticleProtein BindingSignal TransductionGRP78Protein Disulfide-Isomerase FamilyCell SurvivalTH tyrosine hydroxylasePrimary Cell CultureSCG superior cervical ganglionProtein Disulfide-IsomerasesIRE1 inositol-requiring enzyme 1ER-STRESSER endoplasmic reticulum03 medical and health sciencesohjelmoitunut solukuolemaC-MANF C-terminal domain of MANFCSPs chemical shift perturbationsAnimalsHumansHSP70 Heat-Shock ProteinsNerve Growth FactorsNBD nucleotide-binding domainNMR nuclear magnetic resonanceMolecular Biology030102 biochemistry & molecular biologyBIPATF6Dopaminergic NeuronsGene Expression ProfilingBinding proteinneuronal cell deathDISSOCIATIONCell BiologyNEI nucleotide exchange inhibitorEmbryo MammalianadenosiinitrifosfaattiATPhermosolutmesencephalic astrocyte-derived neurotrophic factorprotein–protein interactionPERK protein kinase RNA-like ER kinaseHEK293 Cells030104 developmental biologyGene Expression RegulationChaperone (protein)Tg thapsigarginbiology.proteinUnfolded protein responseAP-MS affinity purification mass spectrometry1182 Biochemistry cell and molecular biologyGFP-SH SH-tagged GFPendoplasmic reticulum stress (ER stress)DA dopaminemesencephalic astrocyte-derived neurotrophic factor (MANF)proteiinitNeuroplastin
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Effects of nucleotide binding to LmrA: A combined MAS-NMR and solution NMR study

2015

ABC transporters are fascinating examples of fine-tuned molecular machines that use the energy from ATP hydrolysis to translocate a multitude of substrates across biological membranes. While structural details have emerged on many members of this large protein superfamily, a number of functional details are still under debate. High resolution structures yield valuable insights into protein function, but it is the combination of structural, functional and dynamic insights that facilitates a complete understanding of the workings of their complex molecular mechanisms. NMR is a technique well-suited to investigate proteins in atomic resolution while taking their dynamic properties into account…

Magnetic Resonance SpectroscopyBiophysicsATP-binding cassette transporterProtein dynamicsCrystallography X-RayBiochemistryLmrABacterial ProteinsNucleotide bindingMagic angle spinningSolution NMRNucleotidesChemistryWalker motifsCell BiologyNuclear magnetic resonance spectroscopyProtein superfamilyBiochemistryCyclic nucleotide-binding domainBiophysicsMAS NMRABC transporterMultidrug Resistance-Associated ProteinsMultidrug Resistance-Associated ProteinsHeteronuclear single quantum coherence spectroscopyProtein BindingBiochimica et Biophysica Acta (BBA) - Biomembranes
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The Spodoptera exigua ABCC2 Acts as a Cry1A Receptor Independently of its Nucleotide Binding Domain II

2019

ABC proteins are primary-active transporters that require the binding and hydrolysis of ATP to transport substrates across the membrane. Since the first report of an ABCC2 transporter as receptor of Cry1A toxins, the number of ABC transporters known to be involved in the mode of action of Cry toxins has increased. In Spodoptera exigua, a mutation in the SeABCC2 gene is described as genetically linked to resistance to the Bt-product XentariTM. This mutation affects an intracellular domain involved in ATP binding, but not the extracellular loops. We analyzed whether this mutation affects the role of the SeABCC2 as a functional receptor to Cry1A toxins. The results show that Sf21 cells express…

0106 biological sciencesCell SurvivalHealth Toxicology and Mutagenesislcsh:MedicineReceptors Cell SurfaceATP-binding cassette transporterSpodopteraSpodopteraToxicologymedicine.disease_causeBt resistance01 natural sciencesArticleCell LineHemolysin Proteins03 medical and health sciencesBacterial Proteinsmode of actionGTP-Binding ProteinsATP hydrolysismedicineAnimalsReceptor030304 developmental biology0303 health sciencesMutationBacillus thuringiensis ToxinsbiologyChemistryfungilcsh:Rheterologous expressionTransporterbiology.organism_classificationMultidrug Resistance-Associated Protein 2Cell biologyEndotoxins010602 entomologyCyclic nucleotide-binding domainSf21 cellstruncated transporterInsect ProteinsHeterologous expressionMultidrug Resistance-Associated ProteinsToxins
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What monomeric nucleotide binding domains can teach us about dimeric ABC proteins

2020

The classic conceptualization of ATP binding cassette (ABC) transporter function is an ATP-dependent conformational change coupled to transport of a substrate across a biological membrane via the transmembrane domains (TMDs). The binding of two ATP molecules within the transporter's two nucleotide binding domains (NBDs) induces their dimerization. Despite retaining the ability to bind nucleotides, isolated NBDs frequently fail to dimerize. ABC proteins without a TMD, for example ABCE and ABCF, have NBDs tethered via elaborate linkers, further supporting that NBD dimerization does not readily occur for isolated NBDs. Intriguingly, even in full-length transporters, the NBD-dimerized, outward-…

Conformational changeBiophysicsContext (language use)ATP-binding cassette transporterBiochemistry03 medical and health sciencesAdenosine TriphosphateProtein DomainsStructural BiologyGeneticsAnimalsHumansNucleotideMolecular Biology030304 developmental biologychemistry.chemical_classification0303 health sciencesBinding Sites030302 biochemistry & molecular biologyTransporterBiological membraneCell BiologyTransmembrane domainchemistryCyclic nucleotide-binding domainBiophysicsATP-Binding Cassette Transporterslipids (amino acids peptides and proteins)Protein MultimerizationProtein BindingFEBS Letters
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Crystal structure of human gamma-butyrobetaine hydroxylase.

2010

Gamma-butyrobetaine hydroxylase (GBBH) is a 2-ketoglutarate-dependent dioxygenase that catalyzes the biosynthesis of l-carnitine by hydroxylation of gamma-butyrobetaine (GBB). l-carnitine is required for the transport of long-chain fatty acids into mitochondria for generating metabolic energy. The only known synthetic inhibitor of GBBH is mildronate (3-(2,2,2-trimethylhydrazinium) propionate dihydrate), which is a non-hydroxylatable analog of GBB. To aid in the discovery of novel GBBH inhibitors by rational drug design, we have solved the three-dimensional structure of recombinant human GBBH at 2.0A resolution. The GBBH monomer consists of a catalytic double-stranded beta-helix (DBSH) domai…

EGF-like domainStereochemistrygamma-Butyrobetaine DioxygenaseBiophysicsDrug designBiochemistryHydroxylationchemistry.chemical_compoundDioxygenaseCatalytic DomainHumansEnzyme InhibitorsMolecular BiologyHistidinechemistry.chemical_classificationCrystallographybiologyActive siteCell BiologyRecombinant ProteinsZincEnzymeBiochemistrychemistryCyclic nucleotide-binding domainDrug Designbiology.proteinProtein MultimerizationMethylhydrazinesBiochemical and biophysical research communications
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