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- PDB-2llm: Structure of amyloid precursor protein's transmembrane domain -

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Basic information

Entry
Database: PDB / ID: 2llm
TitleStructure of amyloid precursor protein's transmembrane domain
ComponentsAmyloid beta A4 protein
KeywordsPROTEIN FIBRIL / Alzheimer's disease
Function / homology
Function and homology information


regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity ...regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / smooth endoplasmic reticulum calcium ion homeostasis / axon midline choice point recognition / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / NMDA selective glutamate receptor signaling pathway / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / positive regulation of amyloid fibril formation / neuron remodeling / : / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / suckling behavior / nuclear envelope lumen / dendrite development / COPII-coated ER to Golgi transport vesicle / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / The NLRP3 inflammasome / regulation of presynapse assembly / transition metal ion binding / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / intracellular copper ion homeostasis / negative regulation of neuron differentiation / ECM proteoglycans / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / protein serine/threonine kinase binding / positive regulation of chemokine production / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / forebrain development / Notch signaling pathway / Mitochondrial protein degradation / neuron projection maintenance / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / cholesterol metabolic process / positive regulation of mitotic cell cycle / response to interleukin-1 / adult locomotory behavior / extracellular matrix organization / axonogenesis / platelet alpha granule lumen / trans-Golgi network membrane / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / learning / positive regulation of interleukin-1 beta production / positive regulation of long-term synaptic potentiation / locomotory behavior / central nervous system development / endosome lumen / astrocyte activation / positive regulation of JNK cascade / Post-translational protein phosphorylation / synapse organization / regulation of long-term neuronal synaptic plasticity / microglial cell activation / TAK1-dependent IKK and NF-kappa-B activation / visual learning / serine-type endopeptidase inhibitor activity / neuromuscular junction / recycling endosome / cognition / neuron cellular homeostasis / Golgi lumen / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / cellular response to amyloid-beta / G2/M transition of mitotic cell cycle / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle
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, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal ...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, 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. / Amyloid precursor protein (APP) E1 domain profile. / Amyloid precursor protein (APP) E2 domain profile. / Amyloidogenic glycoprotein, extracellular / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, E2 domain / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / Amyloid A4 N-terminal heparin-binding / E2 domain of amyloid precursor protein / 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.D. / Bocharova, O.V. / Bocharov, E.V. / Arseniev, A.S.
CitationJournal: Acta Naturae / Year: 2011
Title: Structural and dynamic study of the transmembrane domain of the amyloid precursor protein.
Authors: Nadezhdin, K.D. / Bocharova, O.V. / Bocharov, E.V. / Arseniev, A.S.
History
DepositionNov 15, 2011Deposition site: BMRB / Processing site: RCSB
Revision 1.0Jun 20, 2012Provider: repository / Type: Initial release
Revision 1.1Jun 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 1.2May 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: Amyloid beta A4 protein


Theoretical massNumber of molelcules
Total (without water)4,4501
Polymers4,4501
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)20 / 20structures with the least restraint violations
RepresentativeModel #1fewest violations

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Components

#1: Protein/peptide Amyloid beta A4 protein / ABPP / APPI / APP / Alzheimer disease amyloid protein / Cerebral vascular amyloid peptide / CVAP / ...ABPP / APPI / APP / Alzheimer disease amyloid protein / Cerebral vascular amyloid peptide / CVAP / PreA4 / Protease nexin-II / PN-II / N-APP / Soluble APP-alpha / S-APP-alpha / Soluble APP-beta / S-APP-beta / C99 / Beta-amyloid protein 42 / Beta-APP42 / Beta-amyloid protein 40 / Beta-APP40 / C83 / P3(42) / P3(40) / C80


Mass: 4450.460 Da / Num. of mol.: 1 / 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) / 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
1212D 1H-13C HSQC
1313D HNCO
1413D HNCA
1513D HN(CO)CA
1613D (H)CCH-TOCSY
1713D 1H-13C NOESY aliphatic
1822D 1H-15N HSQC
1923D 1H-15N NOESY
11023D 1H-15N TOCSY

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Sample preparation

Details
Solution-IDContentsSolvent system
10.3-1 mM [U-100% 13C; U-100% 15N] APPjmtm, 21-70 mM [U-100% 2H] DPC, 95% H2O/5% D2O95% H2O/5% D2O
20.3-1 mM [U-100% 15N] APPjmtm, 21-70 mM DPC, 95% H2O/5% D2O95% H2O/5% D2O
Sample
UnitsComponentIsotopic labelingConc. range (mg/ml)Solution-ID
mMAPPjmtm-1[U-100% 13C; U-100% 15N]0.3-11
mMDPC-2[U-100% 2H]21-701
mMAPPjmtm-3[U-100% 15N]0.3-12
mMDPC-421-702
Sample conditionsIonic strength: 20 / pH: 4.6 / Pressure: ambient / Temperature: 318 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker AvanceBrukerAVANCE6001
Bruker AvanceBrukerAVANCE8002

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Processing

NMR software
NameVersionDeveloperClassification
TopSpinBruker Biospincollection
TopSpinBruker Biospinprocessing
CYANA2.1Guntert, Mumenthaler and Wuthrichstructure solution
CYANA2.1Guntert, Mumenthaler and Wuthrichrefinement
MOLMOLKoradi, Billeter and Wuthrichgeometry optimization
MOLMOLKoradi, Billeter and Wuthrichvisualization
TALOS+Cornilescu, Delaglio and Baxrefinement
TALOS+Cornilescu, Delaglio and Baxstructure solution
CARAR.L.J.Kellerchemical shift assignment
CARAR.L.J.Kellerdata analysis
CARAR.L.J.Kellerpeak picking
RefinementMethod: simulated annealing / Software ordinal: 1
NMR representativeSelection criteria: fewest violations
NMR ensembleConformer selection criteria: structures with the least restraint violations
Conformers calculated total number: 20 / Conformers submitted total number: 20

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