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- PDB-2loh: Dimeric structure of transmembrane domain of amyloid precursor pr... -

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Basic information

Entry
Database: PDB / ID: 2loh
TitleDimeric structure of transmembrane domain of amyloid precursor protein in micellar environment
ComponentsP3(42)
KeywordsNEUROPEPTIDE
Function / homology
Function and homology information


amyloid-beta complex / growth cone lamellipodium / cellular response to norepinephrine stimulus / collateral sprouting in absence of injury / growth cone filopodium / microglia development / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / regulation of Wnt signaling pathway / axon midline choice point recognition ...amyloid-beta complex / growth cone lamellipodium / cellular response to norepinephrine stimulus / collateral sprouting in absence of injury / growth cone filopodium / microglia development / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / regulation of Wnt signaling pathway / axon midline choice point recognition / regulation of synapse structure or activity / hippocampal neuron apoptotic process / astrocyte activation involved in immune response / NMDA selective glutamate receptor signaling pathway / regulation of spontaneous synaptic transmission / mating behavior / growth factor receptor binding / peptidase activator activity / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / PTB domain binding / positive regulation of amyloid fibril formation / Golgi-associated vesicle / astrocyte projection / Lysosome Vesicle Biogenesis / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / neuron remodeling / nuclear envelope lumen / dendrite development / TRAF6 mediated NF-kB activation / positive regulation of protein metabolic process / signaling receptor activator activity / negative regulation of long-term synaptic potentiation / Advanced glycosylation endproduct receptor signaling / transition metal ion binding / The NLRP3 inflammasome / modulation of excitatory postsynaptic potential / main axon / intracellular copper ion homeostasis / regulation of multicellular organism growth / ECM proteoglycans / response to insulin-like growth factor stimulus / positive regulation of T cell migration / regulation of presynapse assembly / neuronal dense core vesicle / Purinergic signaling in leishmaniasis infection / cellular response to manganese ion / positive regulation of chemokine production / Notch signaling pathway / swimming behavior / neuron projection maintenance / extracellular matrix organization / clathrin-coated pit / positive regulation of mitotic cell cycle / axonogenesis / Mitochondrial protein degradation / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / platelet alpha granule lumen / astrocyte activation / response to interleukin-1 / regulation of neuron apoptotic process / cellular response to cAMP / cellular response to copper ion / positive regulation of glycolytic process / endosome lumen / trans-Golgi network membrane / positive regulation of interleukin-1 beta production / protein serine/threonine kinase binding / dendritic shaft / positive regulation of long-term synaptic potentiation / learning / central nervous system development / Post-translational protein phosphorylation / adult locomotory behavior / serine-type endopeptidase inhibitor activity / locomotory behavior / microglial cell activation / cellular response to nerve growth factor stimulus / TAK1-dependent IKK and NF-kappa-B activation / positive regulation of non-canonical NF-kappaB signal transduction / synapse organization / visual learning / recycling endosome / positive regulation of interleukin-6 production / positive regulation of JNK cascade / Golgi lumen / regulation of long-term neuronal synaptic plasticity / response to lead ion / cognition / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / cellular response to amyloid-beta / endocytosis / neuron projection development / positive regulation of tumor necrosis factor production / positive regulation of inflammatory response / calcium ion transport / Platelet degranulation / regulation of translation / heparin binding / regulation of gene expression
Similarity search - Function
Single alpha-helices involved in coiled-coils or other helix-helix interfaces - #1670 / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, heparin-binding / Amyloid A4 N-terminal heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) ...Single alpha-helices involved in coiled-coils or other helix-helix interfaces - #1670 / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, heparin-binding / Amyloid A4 N-terminal heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, intracellular domain, conserved site / Beta-amyloid precursor protein C-terminus / Amyloid precursor protein (APP) intracellular domain signature. / Amyloidogenic glycoprotein, extracellular / Amyloidogenic glycoprotein, E2 domain / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / E2 domain of amyloid precursor protein / Amyloid precursor protein (APP) E1 domain profile. / Amyloid precursor protein (APP) E2 domain profile. / amyloid A4 / Amyloidogenic glycoprotein / Proteinase inhibitor I2, Kunitz, conserved site / Pancreatic trypsin inhibitor (Kunitz) family signature. / BPTI/Kunitz family of serine protease inhibitors. / Pancreatic trypsin inhibitor Kunitz domain / Kunitz/Bovine pancreatic trypsin inhibitor domain / Pancreatic trypsin inhibitor (Kunitz) family profile. / Pancreatic trypsin inhibitor Kunitz domain superfamily / Single alpha-helices involved in coiled-coils or other helix-helix interfaces / Helix non-globular / Special / PH-like domain superfamily
Similarity search - Domain/homology
Amyloid-beta precursor protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / simulated annealing
Model detailsfewest violations, model 1
AuthorsNadezhdin, K. / Bocharov, E. / Bocharova, O. / Arseniev, A.
CitationJournal: Febs Lett. / Year: 2012
Title: Dimeric structure of transmembrane domain of amyloid precursor protein in micellar environment.
Authors: Nadezhdin, K.D. / Bocharova, O.V. / Bocharov, E.V. / Arseniev, A.S.
History
DepositionJan 24, 2012Deposition site: BMRB / Processing site: RCSB
Revision 1.0May 23, 2012Provider: repository / Type: Initial release
Revision 1.1Jul 11, 2012Group: Database references
Revision 1.2Jun 14, 2023Group: Data collection / Database references / Other
Category: database_2 / pdbx_database_status ...database_2 / pdbx_database_status / pdbx_nmr_software / pdbx_nmr_spectrometer / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_nmr_data / _pdbx_nmr_software.name / _pdbx_nmr_spectrometer.model / _struct_ref_seq_dif.details
Revision 1.3May 15, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 / Item: _database_2.pdbx_DOI

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: P3(42)
B: P3(42)


Theoretical massNumber of molelcules
Total (without water)8,9012
Polymers8,9012
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)12 / 100target function
RepresentativeModel #1fewest violations

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Components

#1: Protein/peptide P3(42) / Amyloid beta A4 protein


Mass: 4450.460 Da / Num. of mol.: 2 / Fragment: UNP residues 686-726
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: APP, A4, AD1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)pLysS / References: UniProt: P05067

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1112D 1H-15N HSQC
1213D 1H-15N NOESY
1322D 1H-15N HSQC
1423D HNCO
1523D HN(CO)CA
1623D 1H-13C NOESY aliphatic
1723D HNCA
1823D (H)CCH-TOCSY
1923D 15N,13C-F1-filtered/F3-edited NOESY
11022D 1H-13C HSQC

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Sample preparation

Details
Solution-IDContentsSolvent system
10.9 mM [U-100% 15N] APPjmtm, 36 mM DPC, 95% H2O/5% D2O95% H2O/5% D2O
20.75 mM [U-100% 13C; U-100% 15N] APPjmtm, 0.75 mM APPjmtm, 60 mM [U-98% 2H] DPC, 100% D2O100% D2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
0.9 mMAPPjmtm-1[U-100% 15N]1
36 mMDPC-21
0.75 mMAPPjmtm-3[U-100% 13C; U-100% 15N]2
0.75 mMAPPjmtm-42
60 mMDPC-5[U-98% 2H]2
Sample conditionsIonic strength: 20 / pH: 6.2 / Pressure: ambient / Temperature: 318 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker Avance IIIBrukerAVANCE III6001
Bruker Avance IIIBrukerAVANCE III8002

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Processing

NMR software
NameVersionDeveloperClassification
CARA1.8.4Keller,Bettendorff,Dambergerpeak picking
CARA1.8.4Keller,Bettendorff,Dambergerchemical shift assignment
CARA1.8.4Keller,Bettendorff,Dambergerpeak integration
TopSpinBruker Biospincollection
TopSpinBruker Biospinprocessing
TopSpinBruker Biospindata analysis
CYANA3Peter Guentertstructure solution
CYANA3Peter Guentertprocessing
MOLMOLKoradi, Billeter and Wuthrichgeometry optimization
MOLMOLKoradi, Billeter and Wuthrichvisualization
TALOSCornilescu, Delaglio and Baxdihedral angles prediction
CYANAPeter Guentertrefinement
RefinementMethod: simulated annealing / Software ordinal: 1
NMR representativeSelection criteria: fewest violations
NMR ensembleConformer selection criteria: target function / Conformers calculated total number: 100 / Conformers submitted total number: 12

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