[English] 日本語
Yorodumi
- PDB-4mvl: Crystal structure of an engineered lipocalin (Anticalin H1GA) in ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4mvl
TitleCrystal structure of an engineered lipocalin (Anticalin H1GA) in complex with the Alzheimer amyloid peptide Abeta1-40
Components
  • Beta-amyloid protein 40
  • Neutrophil gelatinase-associated lipocalin
KeywordsPROTEIN BINDING/PROTEIN FIBRIL / beta-barrel / engineered lipocalin / binding protein / PROTEIN BINDING-PROTEIN FIBRIL complex
Function / homology
Function and homology information


siderophore transport / Metal sequestration by antimicrobial proteins / regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / iron ion sequestering activity / collateral sprouting in absence of injury / microglia development / regulation of Wnt signaling pathway / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands ...siderophore transport / Metal sequestration by antimicrobial proteins / regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / iron ion sequestering activity / collateral sprouting in absence of injury / microglia development / regulation of Wnt signaling pathway / regulation of synapse structure or activity / 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 / enterobactin binding / 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 / negative regulation of neuron differentiation / intracellular copper ion homeostasis / 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 / response to interleukin-1 / positive regulation of mitotic cell cycle / adult locomotory behavior / axonogenesis / extracellular matrix organization / positive regulation of peptidyl-threonine phosphorylation / platelet alpha granule lumen / trans-Golgi network membrane / dendritic shaft / learning / positive regulation of interleukin-1 beta production / locomotory behavior / positive regulation of long-term synaptic potentiation / central nervous system development / endosome lumen / astrocyte activation / Iron uptake and transport / positive regulation of JNK cascade / Post-translational protein phosphorylation / synapse organization / microglial cell activation / regulation of long-term neuronal synaptic plasticity / 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 / specific granule lumen / cellular response to amyloid-beta / G2/M transition of mitotic cell cycle
Similarity search - Function
Neutrophil gelatinase-associated lipocalin/epididymal-specific lipocalin-12 / 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 / Lipocalin / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide ...Neutrophil gelatinase-associated lipocalin/epididymal-specific lipocalin-12 / 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 / Lipocalin / 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 / Lipocalin family conserved site / 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 / Calycin beta-barrel core domain / Lipocalin / cytosolic fatty-acid binding protein family / Lipocalin/cytosolic fatty-acid binding domain / Calycin / Lipocalin / Lipocalin signature. / PH-like domain superfamily / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
Amyloid-beta precursor protein / Neutrophil gelatinase-associated lipocalin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.3 Å
AuthorsEichinger, A. / Skerra, A.
CitationJournal: Biochem.J. / Year: 2016
Title: High-affinity Anticalins with aggregation-blocking activity directed against the Alzheimer beta-amyloid peptide.
Authors: Rauth, S. / Hinz, D. / Borger, M. / Uhrig, M. / Mayhaus, M. / Riemenschneider, M. / Skerra, A.
History
DepositionSep 24, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 12, 2015Provider: repository / Type: Initial release
Revision 1.1Apr 20, 2016Group: Database references
Revision 1.2Jun 15, 2016Group: Database references
Revision 1.3Sep 20, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Neutrophil gelatinase-associated lipocalin
B: Neutrophil gelatinase-associated lipocalin
C: Neutrophil gelatinase-associated lipocalin
D: Neutrophil gelatinase-associated lipocalin
E: Beta-amyloid protein 40
F: Beta-amyloid protein 40
G: Beta-amyloid protein 40
H: Beta-amyloid protein 40


Theoretical massNumber of molelcules
Total (without water)103,1408
Polymers103,1408
Non-polymers00
Water2,324129
1
A: Neutrophil gelatinase-associated lipocalin
E: Beta-amyloid protein 40


Theoretical massNumber of molelcules
Total (without water)25,7852
Polymers25,7852
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1580 Å2
ΔGint-7 kcal/mol
Surface area10330 Å2
MethodPISA
2
B: Neutrophil gelatinase-associated lipocalin
F: Beta-amyloid protein 40


Theoretical massNumber of molelcules
Total (without water)25,7852
Polymers25,7852
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1410 Å2
ΔGint-8 kcal/mol
Surface area10250 Å2
MethodPISA
3
C: Neutrophil gelatinase-associated lipocalin
G: Beta-amyloid protein 40


Theoretical massNumber of molelcules
Total (without water)25,7852
Polymers25,7852
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1370 Å2
ΔGint-9 kcal/mol
Surface area10360 Å2
MethodPISA
4
D: Neutrophil gelatinase-associated lipocalin
H: Beta-amyloid protein 40


Theoretical massNumber of molelcules
Total (without water)25,7852
Polymers25,7852
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1340 Å2
ΔGint-9 kcal/mol
Surface area10350 Å2
MethodPISA
Unit cell
Length a, b, c (Å)79.300, 79.180, 142.590
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein
Neutrophil gelatinase-associated lipocalin / NGAL / 25 kDa alpha-2-microglobulin-related subunit of MMP-9 / Lipocalin-2 / Oncogene 24p3 / ...NGAL / 25 kDa alpha-2-microglobulin-related subunit of MMP-9 / Lipocalin-2 / Oncogene 24p3 / Siderocalin LCN2 / p25


Mass: 21449.244 Da / Num. of mol.: 4 / Fragment: UNP residues 21-198
Mutation: Q28H,L36A,A40V,I41L,Q49L,L70G,R72D,K73D,D77L,W79K,C87S,N96R,Y100E,L103G,Y106W,K125E,S127A,Y132T,K134N
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: engineered variant H1GA, HNL, LCN2, LCN2 (NGAL_HUMAN), NGAL
Plasmid: pNGAL98-H1GA / Production host: Escherichia coli (E. coli) / Strain (production host): JM83 / References: UniProt: P80188
#2: Protein/peptide
Beta-amyloid protein 40 / Beta-APP40


Mass: 4335.852 Da / Num. of mol.: 4 / Fragment: UNP residues 672-711 / Source method: obtained synthetically
Details: The Abeta(1-40) peptide was synthesized without modifications.
Source: (synth.) Homo sapiens (human) / References: UniProt: P05067
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 129 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.17 Å3/Da / Density % sol: 43.32 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 24 % (w/v) PEG 3350, pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.91841 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Dec 2, 2010 / Details: mirrors
RadiationMonochromator: Si 111 crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91841 Å / Relative weight: 1
Reflection twin
Crystal-IDIDOperatorDomain-IDFraction
11H, K, L10.516
11K, H, -L20.484
ReflectionResolution: 2.3→71.295 Å / Num. all: 39966 / Num. obs: 39966 / % possible obs: 98.4 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 2 / Redundancy: 5.9 % / Rsym value: 0.088 / Net I/σ(I): 13.9
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRsym value% possible all
2.3-2.425.50.2243.43045555380.22495.3
2.42-2.575.50.1774.32933453650.17797
2.57-2.755.50.14352834451170.14398.3
2.75-2.975.70.1066.62736748180.10698.9
2.97-3.255.80.0847.72562344500.08499.5
3.25-3.645.90.0788.12397640730.07899.5
3.64-4.26.20.0857.42262436490.08599.9
4.2-5.146.70.0847.32066330700.084100
5.14-7.2770.0648.71710824560.064100
7.27-39.656.40.0588.9922014300.05899.4

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
MOSFLMdata reduction
SCALA3.3.16data scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACT3.11data extraction
MAR345dtbdata collection
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 4GH7

4gh7


Resolution: 2.3→71.295 Å / Cor.coef. Fo:Fc: 0.878 / Cor.coef. Fo:Fc free: 0.833 / WRfactor Rfree: 0.2866 / WRfactor Rwork: 0.223 / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.7508 / SU B: 14.2 / SU ML: 0.172 / SU R Cruickshank DPI: 0.0719 / SU Rfree: 0.0555 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.072 / ESU R Free: 0.055 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.2794 2026 5.1 %RANDOM
Rwork0.219 ---
all0.2221 39966 --
obs0.219 39844 97.57 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 69.09 Å2 / Biso mean: 26.1626 Å2 / Biso min: 2.25 Å2
Baniso -1Baniso -2Baniso -3
1--14.53 Å2-0 Å2-0 Å2
2---3.37 Å20 Å2
3---17.9 Å2
Refinement stepCycle: LAST / Resolution: 2.3→71.295 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5864 0 0 129 5993
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0060.026012
X-RAY DIFFRACTIONr_angle_refined_deg1.0241.9588142
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.6365722
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.5424.602289
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.882151027
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.8711528
X-RAY DIFFRACTIONr_chiral_restr0.0670.2883
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0214588
LS refinement shellResolution: 2.3→2.356 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.294 123 -
Rwork0.208 2469 -
all-2592 -
obs--88.13 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.8833-0.0464-0.04240.3296-0.04620.5899-0.00550.04840.0413-0.0120.0025-0.0016-0.0055-0.01690.0030.1122-0.00140.00130.08460.02080.0063-19.005721.8816-6.1139
20.69110.24860.05510.6871-0.17920.8867-0.02530.0492-0.0496-0.10130.02550.0070.07380.0054-0.00020.1657-0.00550.00510.08870.0020.0054-26.1581-9.51822.187
30.8583-0.00850.13990.69040.10320.78480.0549-0.08680.00710.0652-0.03890.08430.0243-0.0293-0.0160.157-0.01190.00040.1294-0.00530.012-30.0435-5.7567-37.1371
40.25050.0110.10151.082-0.2160.7954-0.02590.01020.0108-0.0215-0.0073-0.11320.05820.03070.03320.1342-0.0045-0.01170.08570.00220.01395.72841.6843-30.8951
50.4447-0.4222-0.98712.72110.97672.19580.04820.11880.0265-0.06460.0086-0.0504-0.1307-0.2534-0.05680.15280.0263-0.00420.13750.03420.0109-24.358928.827-8.319
61.10782.25260.94576.142-0.43544.39420.03740.1823-0.32810.0480.451-0.52640.1535-0.0018-0.48850.2443-0.00320.01750.1607-0.04140.1146-30.4839-17.66592.0946
70.45570.8321-0.31071.6771-0.61470.22620.21180.04520.26030.2591-0.0120.5906-0.101-0.0007-0.19990.25920.00990.03730.1925-0.05060.2331-35.8598-11.48-37.5246
82.53551.46470.97430.84620.5875.41280.00950.0407-0.18090.00730.0209-0.105-0.1712-0.0887-0.03040.14070.0234-0.0030.0975-0.01120.035310.5962-4.383-29.7676
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A5 - 177
2X-RAY DIFFRACTION2B6 - 177
3X-RAY DIFFRACTION3C5 - 178
4X-RAY DIFFRACTION4D7 - 177
5X-RAY DIFFRACTION5E17 - 27
6X-RAY DIFFRACTION6F17 - 27
7X-RAY DIFFRACTION7G18 - 26
8X-RAY DIFFRACTION8H18 - 26

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more