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- PDB-9px5: Crystal structure of Fab 7268 in complex with MBP-TREM2 Ig domain... -

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Basic information

Entry
Database: PDB / ID: 9px5
TitleCrystal structure of Fab 7268 in complex with MBP-TREM2 Ig domain fusion
Components
  • 7268 Fab Heavy Chain
  • 7268 Fab Light Chain
  • Maltose/maltodextrin-binding periplasmic protein,Triggering receptor expressed on myeloid cells 2
KeywordsIMMUNE SYSTEM / Fab / antibody / complex
Function / homology
Function and homology information


positive regulation of high-density lipoprotein particle clearance / regulation of toll-like receptor 6 signaling pathway / positive regulation of complement activation, classical pathway / detection of lipoteichoic acid / regulation of macrophage inflammatory protein 1 alpha production / regulation of hippocampal neuron apoptotic process / regulation of plasma membrane bounded cell projection organization / positive regulation of C-C chemokine receptor CCR7 signaling pathway / excitatory synapse pruning / positive regulation of CD40 signaling pathway ...positive regulation of high-density lipoprotein particle clearance / regulation of toll-like receptor 6 signaling pathway / positive regulation of complement activation, classical pathway / detection of lipoteichoic acid / regulation of macrophage inflammatory protein 1 alpha production / regulation of hippocampal neuron apoptotic process / regulation of plasma membrane bounded cell projection organization / positive regulation of C-C chemokine receptor CCR7 signaling pathway / excitatory synapse pruning / positive regulation of CD40 signaling pathway / negative regulation of triglyceride storage / negative regulation of cell activation / detection of peptidoglycan / positive regulation of macrophage fusion / import into cell / sulfatide binding / negative regulation of macrophage colony-stimulating factor signaling pathway / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / negative regulation of fat cell proliferation / lipoteichoic acid binding / positive regulation of engulfment of apoptotic cell / positive regulation of establishment of protein localization / positive regulation of synapse pruning / microglial cell activation involved in immune response / negative regulation of toll-like receptor 2 signaling pathway / negative regulation of autophagic cell death / respiratory burst after phagocytosis / negative regulation of astrocyte activation / positive regulation of CAMKK-AMPK signaling cascade / semaphorin receptor binding / positive regulation of low-density lipoprotein particle clearance / positive regulation of microglial cell migration / apolipoprotein A-I binding / detection of lipopolysaccharide / Other semaphorin interactions / T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / CXCL12-activated CXCR4 signaling pathway / negative regulation of toll-like receptor 4 signaling pathway / negative regulation of neuroinflammatory response / high-density lipoprotein particle binding / negative regulation of p38MAPK cascade / very-low-density lipoprotein particle binding / cellular response to oxidised low-density lipoprotein particle stimulus / negative regulation of glial cell apoptotic process / complement-mediated synapse pruning / dendritic cell differentiation / microglial cell proliferation / semaphorin receptor complex / positive regulation of microglial cell activation / phagocytosis, recognition / low-density lipoprotein particle binding / amyloid-beta clearance by cellular catabolic process / negative regulation of NLRP3 inflammasome complex assembly / cellular response to lipoprotein particle stimulus / regulation of TOR signaling / regulation of resting membrane potential / positive regulation of phagocytosis, engulfment / cellular response to peptidoglycan / peptidoglycan binding / regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / positive regulation of chemotaxis / positive regulation of amyloid-beta clearance / positive regulation of potassium ion transport / semaphorin receptor activity / phosphatidylethanolamine binding / positive regulation of proteasomal protein catabolic process / positive regulation of osteoclast differentiation / negative regulation of amyloid fibril formation / cellular response to lipid / kinase activator activity / regulation of interleukin-6 production / apoptotic cell clearance / dendritic spine maintenance / negative regulation of interleukin-1 beta production / phagocytosis, engulfment / regulation of innate immune response / phosphatidylserine binding / negative regulation of cholesterol storage / pyroptotic inflammatory response / detection of maltose stimulus / regulation of cytokine production involved in inflammatory response / lipid homeostasis / maltose transport complex / cellular response to lipoteichoic acid / amyloid-beta clearance / carbohydrate transport / positive regulation of ATP biosynthetic process / lipoprotein particle binding / positive regulation of intracellular signal transduction / humoral immune response / regulation of lipid metabolic process / positive regulation of interleukin-10 production / apolipoprotein binding / plasma membrane raft / negative regulation of tumor necrosis factor production / positive regulation of cholesterol efflux / social behavior / carbohydrate transmembrane transporter activity / maltose binding / positive regulation of TOR signaling
Similarity search - Function
: / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Maltose/maltodextrin-binding periplasmic protein / Triggering receptor expressed on myeloid cells 2
Similarity search - Component
Biological speciesEscherichia coli (E. coli)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.7 Å
AuthorsArndt, J.W. / Chao, Q. / Cooke, H.A. / Almeida, A.D.S.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: Mabs / Year: 2025
Title: Building a potent TREM2 agonistic, biparatopic, common light chain antibody.
Authors: da Silva Almeida, A. / Geddie, M.L. / Bhate, A. / Quan, C. / Arndt, J.W. / Jiao, Y. / Santoro, J.C. / Noiman, L. / Vijayakumar, R. / Sanchez-Salazar, J. / Datta, A. / Antognetti, G. / ...Authors: da Silva Almeida, A. / Geddie, M.L. / Bhate, A. / Quan, C. / Arndt, J.W. / Jiao, Y. / Santoro, J.C. / Noiman, L. / Vijayakumar, R. / Sanchez-Salazar, J. / Datta, A. / Antognetti, G. / Hartana, C.A. / Wang, X.F. / Smith, B.A. / Bartlett, D. / Duncan, D. / Liu, C.C. / Otero Gutierrez, K. / Cameron, T.O. / Koirala, S. / Cooke, H.A.
History
DepositionAug 5, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 10, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Maltose/maltodextrin-binding periplasmic protein,Triggering receptor expressed on myeloid cells 2
H: 7268 Fab Heavy Chain
L: 7268 Fab Light Chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)102,1516
Polymers101,6173
Non-polymers5343
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)119.900, 64.230, 160.800
Angle α, β, γ (deg.)90.00, 94.45, 90.00
Int Tables number5
Space group name H-MC121

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Components

#1: Protein Maltose/maltodextrin-binding periplasmic protein,Triggering receptor expressed on myeloid cells 2


Mass: 54172.066 Da / Num. of mol.: 1 / Fragment: Ig domain of TREM-2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human)
Gene: malE, b4034, JW3994, TREM2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0AEX9, UniProt: Q9NZC2
#2: Antibody 7268 Fab Heavy Chain


Mass: 24081.043 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#3: Antibody 7268 Fab Light Chain


Mass: 23363.852 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#4: Polysaccharide alpha-D-glucopyranose-(1-4)-beta-D-glucopyranose


Type: oligosaccharide / Mass: 342.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source
DescriptorTypeProgram
DGlcpa1-4DGlcpb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,2,1/[a2122h-1b_1-5][a2122h-1a_1-5]/1-2/a4-b1WURCSPDB2Glycan 1.1.0
[][b-D-Glcp]{[(4+1)][a-D-Glcp]{}}LINUCSPDB-CARE
#5: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 3.04 Å3/Da / Density % sol: 59.51 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6 / Details: 11% PEG 8000, 240mM ammonium sulfate, 100mM MES

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1.000039 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Apr 9, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.000039 Å / Relative weight: 1
ReflectionResolution: 3.7→50 Å / Num. obs: 13219 / % possible obs: 99.21 % / Redundancy: 7.1 % / CC1/2: 0.85 / Net I/σ(I): 5.3
Reflection shellResolution: 3.7→4 Å / Num. unique obs: 2514 / CC1/2: 0.73

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Processing

Software
NameVersionClassification
PHENIX1.21.2-5419_1692refinement
Aimlessdata scaling
XDSdata reduction
MOLREPphasing
PDB_EXTRACTdata extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.7→47.05 Å / SU ML: 0.57 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 30.42 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2682 663 5.02 %
Rwork0.248 --
obs0.2489 13219 99.21 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.7→47.05 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6564 0 33 0 6597
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0026759
X-RAY DIFFRACTIONf_angle_d0.4919283
X-RAY DIFFRACTIONf_dihedral_angle_d10.4892244
X-RAY DIFFRACTIONf_chiral_restr0.041076
X-RAY DIFFRACTIONf_plane_restr0.0041206
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.7-3.990.3771330.34592514X-RAY DIFFRACTION99
3.99-4.390.30791310.27342488X-RAY DIFFRACTION100
4.39-5.020.26831310.23092481X-RAY DIFFRACTION99
5.02-6.320.26681320.24982517X-RAY DIFFRACTION99
6.32-47.050.22491360.21872556X-RAY DIFFRACTION98

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