PDB-2li9: Metal binding domain of rat beta-amyloid

Basic information

• Entry: Database: PDB / ID: 2li9
• Title: Metal binding domain of rat beta-amyloid
• Components: Amyloid beta A4 protein
• Keywords: CELL ADHESION / Alzheimer's disease / Dimer formation / Zinc binding

Function / homology

Function:

Formyl peptide receptors bind formyl peptides and many other ligands / ECM proteoglycans / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / TAK1-dependent IKK and NF-kappa-B activation / positive regulation of protein import / cytosolic mRNA polyadenylation / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Post-translational protein phosphorylation / regulation of neurotransmitter uptake / regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway / positive regulation of response to endoplasmic reticulum stress / negative regulation of presynapse assembly / Mitochondrial protein degradation / smooth endoplasmic reticulum calcium ion homeostasis / positive regulation of gene expression, epigenetic / Platelet degranulation / endosome to plasma membrane transport vesicle / low-density lipoprotein particle mediated signaling / phospholipase D-activating G protein-coupled receptor signaling pathway / regulation of dendritic spine maintenance / negative regulation of blood circulation / positive regulation of endothelin production / positive regulation of Toll signaling pathway / positive regulation of G protein-coupled receptor internalization / regulation of toll-like receptor signaling pathway / positive regulation of long-term synaptic depression / protein trimerization / Lysosome Vesicle Biogenesis / positive regulation of amyloid precursor protein catabolic process / lipoprotein particle / regulation of amyloid-beta clearance / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / intermediate-density lipoprotein particle / synaptic assembly at neuromuscular junction / ciliary rootlet / RAGE receptor binding / regulation of amyloid fibril formation / positive regulation of G protein-coupled receptor signaling pathway / suckling behavior / low-density lipoprotein particle / neuromuscular process controlling balance / high-density lipoprotein particle / very-low-density lipoprotein particle / COPII-coated ER to Golgi transport vesicle / acetylcholine receptor binding / frizzled binding / amyloid-beta complex / growth cone lamellipodium / cellular response to norepinephrine stimulus / collateral sprouting in absence of injury / positive regulation of monocyte chemotaxis / growth cone filopodium / forebrain development / heparan sulfate proteoglycan binding / microglia development / hippocampal neuron apoptotic process / positive regulation of membrane protein ectodomain proteolysis / axo-dendritic transport / axon midline choice point recognition / regulation of synapse structure or activity / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of synaptic transmission, cholinergic / G alpha (q) signalling events / astrocyte activation involved in immune response / negative regulation of neuron differentiation / negative regulation of dendritic spine maintenance / G alpha (i) signalling events / regulation of spontaneous synaptic transmission / mating behavior / negative regulation of protein localization to nucleus / growth factor receptor binding / positive regulation of cAMP/PKA signal transduction / presynaptic active zone / peptidase activator activity / positive regulation of amyloid fibril formation / PTB domain binding / Golgi-associated vesicle / astrocyte projection / neuron remodeling / spindle midzone / dendrite development / regulation of multicellular organism growth / chemoattractant activity / nuclear envelope lumen / intracellular vesicle / smooth endoplasmic reticulum / positive regulation of protein metabolic process / negative regulation of Wnt signaling pathway / signaling receptor activator activity / negative regulation of long-term synaptic potentiation / associative learning / apolipoprotein binding / modulation of excitatory postsynaptic potential / intracellular copper ion homeostasis / Notch signaling pathway / main axon / cholesterol metabolic process / neuron apoptotic process / response to insulin-like growth factor stimulus

Domain/homology:

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 / 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 / PH-like domain superfamily

Component:

Amyloid-beta precursor protein

• Biological species: Rattus norvegicus (Norway rat)
• Method: SOLUTION NMR / simulated annealing, QM, MM geometry optimization
• Model details: closest to the average, model 1
• Authors: Polshakov, V. / Istrate, A. / Kozin, S. / Makarov, A.

Citation

Journal: Biophys.J. / Year: 2012
Title: NMR solution structure of rat Abeta(1-16): toward understanding the mechanism of rats' resistance to Alzheimer's disease.
Authors: Istrate, A.N. / Tsvetkov, P.O. / Mantsyzov, A.B. / Kulikova, A.A. / Kozin, S.A. / Makarov, A.A. / Polshakov, V.I.

#1: Journal: MOL.BIOL.(MOSCOW) / Year: 2010
Title: Optimization of the methods for small peptide solution structure determination by NMR spectroscopy.
Authors: Istrate, A.N. / Mantsyzov, A.B. / Kozin, S.A. / Pol'shakov, V.I.

History

Deposition	Aug 25, 2011	Deposition site: BMRB / Processing site: RCSB
Revision 1.0	Jan 18, 2012	Provider: repository / Type: Initial release
Revision 1.1	Mar 21, 2012	Group: Database references
Revision 1.2	Oct 30, 2024	Group: Data collection / Database references / Derived calculations / Structure summary Category: chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / pdbx_nmr_software / pdbx_nmr_spectrometer / pdbx_struct_conn_angle / struct_conn / struct_ref_seq_dif / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_nmr_software.name / _pdbx_nmr_spectrometer.model / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

Assembly

Deposited unit

A: Amyloid beta A4 protein

B: Amyloid beta A4 protein

hetero molecules

Summary:

• 3.84 kDa, 2 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	3,839	3
Polymers	3,774	2
Non-polymers	65	1
Water	0	0

1

Summary:

• Idetical with deposited unit
• defined by author

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

NMR ensembles

	Data	Criteria
Number of conformers (submitted / calculated)	20 / 40	structures with the lowest energy
Representative	Model #1	closest to the average

Components

#1: Protein/peptide

A B Amyloid beta A4 protein / ABPP / APP / Alzheimer disease amyloid A4 protein homolog / Amyloidogenic glycoprotein / AG

Details:

Mass: 1886.998 Da / Num. of mol.: 2 / Fragment: UNP residues 672-687 / Source method: obtained synthetically / Source: (synth.) Rattus norvegicus (Norway rat) / References: UniProt: P08592

#2: Chemical

A-18 ChemComp-ZN / ZINC ION

Details:

Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn

• Has protein modification: Y

Experimental details

Experiment

• Experiment: Method: SOLUTION NMR; Details: NMR solution structure of the dimer of rat beta-Amyloid metal binding domain complexed with zinc ion

NMR experiment

Conditions-ID	Experiment-ID	Solution-ID	Type
1	1	2	2D 1H-13C HSQC
1	2	1	2D DQF-COSY
1	3	2	2D DQF-COSY
1	4	1	2D 1H-1H NOESY
1	5	2	2D 1H-1H NOESY
1	6	2	2D 1H-1H TOCSY
1	7	1	2D 1H-1H TOCSY

Sample preparation

Details

Solution-ID	Contents	Solvent system
1	5 mM protein_1, 8 mM Zinc cloride, 20 mM [U-100% 2H] TRIS, 0.1 % sodium azide, 90% H2O/10% D2O	90% H2O/10% D2O
2	5 mM protein_1, 8 mM Zinc cloride, 20 mM [U-100% 2H] TRIS, 0.1 % sodium azide, 100% D2O	100% D2O

Sample

Conc. (mg/ml)	Component	Isotopic labeling	Solution-ID
5 mM	entity_1-1		1
8 mM	Zinc cloride-2		1
20 mM	TRIS-3	[U-100% 2H]	1
0.1 %	sodium azide-4		1
5 mM	entity_1-5		2
8 mM	Zinc cloride-6		2
20 mM	TRIS-7	[U-100% 2H]	2
0.1 %	sodium azide-8		2

• Sample conditions: Ionic strength: 10 / pH: 7.1 / Pressure: ambient / Temperature: 278 K

NMR measurement

• NMR spectrometer: Type: Bruker Avance / Manufacturer: Bruker / Model: AVANCE / Field strength: 600 MHz

Processing

NMR software

Name	Version	Developer	Classification
TopSpin		Bruker Biospin	collection
NMRPipe		Delaglio, Grzesiek, Vuister, Zhu, Pfeifer and Bax	processing
Sparky		Goddard	data analysis
Anglesearch		V. Polshakov	data analysis
GROMACS	3.3.1	Van Der Spoel et al.	structure solution
GROMACS/CPMD		Biswas & Gogonea	geometry optimization
ProcheckNMR		Laskowski and MacArthur	data analysis
Insight II		Accelrys Software Inc.	data analysis
GROMACS		Van Der Spoel et al.	refinement
GROMACS/CPMD		Biswas & Gogonea	refinement

• Refinement: Method: simulated annealing, QM, MM geometry optimization / Software ordinal: 1 / Details: simulation in explicit water environment
• NMR constraints: NOE intraresidue total count: 144 / NOE medium range total count: 30 / NOE sequential total count: 66
• NMR representative: Selection criteria: closest to the average
• NMR ensemble: Conformer selection criteria: structures with the lowest energy; Conformers calculated total number: 40 / Conformers submitted total number: 20