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- PDB-8t51: Crystal structure of Fab 3.10C2 bound to TREM2 -

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Basic information

Entry
Database: PDB / ID: 8t51
TitleCrystal structure of Fab 3.10C2 bound to TREM2
Components
  • 3.10C2 Fab heavy chain
  • 3.10C2 Fab light chain
  • Triggering receptor expressed on myeloid cells 2 peptide
KeywordsPEPTIDE BINDING PROTEIN / Antibody / Fab
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 inward rectifier potassium channel activity / positive regulation of C-C chemokine receptor CCR7 signaling pathway / positive regulation of CAMKK-AMPK signaling cascade ...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 inward rectifier potassium channel activity / positive regulation of C-C chemokine receptor CCR7 signaling pathway / positive regulation of CAMKK-AMPK signaling cascade / excitatory synapse pruning / positive regulation of CD40 signaling pathway / negative regulation of cell activation / detection of peptidoglycan / positive regulation of macrophage fusion / import into cell / negative regulation of macrophage colony-stimulating factor signaling pathway / sulfatide binding / positive regulation of engulfment of apoptotic cell / regulation of intracellular signal transduction / 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 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 astrocyte activation / apolipoprotein A-I binding / respiratory burst after phagocytosis / positive regulation of low-density lipoprotein particle clearance / positive regulation of microglial cell migration / negative regulation of autophagic cell death / detection of lipopolysaccharide / Other semaphorin interactions / CXCL12-activated CXCR4 signaling pathway / very-low-density lipoprotein particle binding / negative regulation of p38MAPK cascade / high-density lipoprotein particle binding / negative regulation of neuroinflammatory response / negative regulation of glial cell apoptotic process / negative regulation of toll-like receptor 4 signaling pathway / cellular response to oxidised low-density lipoprotein particle stimulus / regulation of resting membrane potential / dendritic cell differentiation / negative regulation of NLRP3 inflammasome complex assembly / microglial cell proliferation / complement-mediated synapse pruning / positive regulation of microglial cell activation / low-density lipoprotein particle binding / regulation of TOR signaling / amyloid-beta clearance by cellular catabolic process / : / regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / positive regulation of phagocytosis, engulfment / positive regulation of chemotaxis / cellular response to peptidoglycan / phagocytosis, recognition / peptidoglycan binding / positive regulation of proteasomal protein catabolic process / positive regulation of amyloid-beta clearance / phosphatidylethanolamine binding / kinase activator activity / positive regulation of osteoclast differentiation / negative regulation of amyloid fibril formation / cellular response to lipid / positive regulation of kinase activity / apoptotic cell clearance / regulation of interleukin-6 production / negative regulation of interleukin-1 beta production / dendritic spine maintenance / negative regulation of sequestering of triglyceride / phagocytosis, engulfment / positive regulation of ATP biosynthetic process / regulation of innate immune response / negative regulation of cholesterol storage / phosphatidylserine binding / pyroptotic inflammatory response / regulation of cytokine production involved in inflammatory response / lipid homeostasis / plasma membrane raft / lipoprotein particle binding / cellular response to lipoteichoic acid / apolipoprotein binding / social behavior / positive regulation of interleukin-10 production / humoral immune response / negative regulation of tumor necrosis factor production / regulation of lipid metabolic process / positive regulation of TOR signaling / response to axon injury / positive regulation of cholesterol efflux / negative regulation of cytokine production involved in inflammatory response / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of calcium-mediated signaling / negative regulation of canonical NF-kappaB signal transduction / regulation of peptidyl-tyrosine phosphorylation / positive regulation of phagocytosis / negative regulation of inflammatory response to antigenic stimulus / negative regulation of autophagy
Similarity search - Function
Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
ACETATE ION / DI(HYDROXYETHYL)ETHER / Triggering receptor expressed on myeloid cells 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsHsu, P.L. / Wallweber, H.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: To Be Published
Title: Rapid affinity optimization of an anti-TREM2 clinical lead antibody by cross-lineage immune repertoire mining
Authors: Hsiao, Y. / Lin, Z. / Du, C. / Echeverria, A. / Wallweber, H.A. / Aung, T. / Alberstein, R.G. / Shang, Y. / Seeger, F. / Watkins, A. / Seshasayee, D. / Hansen, D.V. / Bolen, C. / Hsu, P.L. / Hotzel, I.
History
DepositionJun 12, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 19, 2024Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: 3.10C2 Fab heavy chain
B: 3.10C2 Fab light chain
C: 3.10C2 Fab heavy chain
D: 3.10C2 Fab light chain
E: Triggering receptor expressed on myeloid cells 2 peptide
F: Triggering receptor expressed on myeloid cells 2 peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)102,72840
Polymers99,8886
Non-polymers2,84034
Water9,584532
1
A: 3.10C2 Fab heavy chain
B: 3.10C2 Fab light chain
C: 3.10C2 Fab heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)73,26826
Polymers71,3643
Non-polymers1,90423
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
D: 3.10C2 Fab light chain
E: Triggering receptor expressed on myeloid cells 2 peptide
F: Triggering receptor expressed on myeloid cells 2 peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,46014
Polymers28,5243
Non-polymers93611
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)66.38, 96.029, 144.316
Angle α, β, γ (deg.)90, 90, 90
Int Tables number18
Space group name H-MP22121
Components on special symmetry positions
IDModelComponents
11A-304-

ZN

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Components

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Protein/peptide , 1 types, 2 molecules EF

#3: Protein/peptide Triggering receptor expressed on myeloid cells 2 peptide / TREM-2 / Triggering receptor expressed on monocytes 2


Mass: 2274.378 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q9NZC2

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Antibody , 2 types, 4 molecules ACBD

#1: Antibody 3.10C2 Fab heavy chain


Mass: 23694.543 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi293 / Production host: Homo sapiens (human)
#2: Antibody 3.10C2 Fab light chain


Mass: 23974.928 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi293 / Production host: Homo sapiens (human)

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Non-polymers , 6 types, 566 molecules

#4: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: SO4
#5: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Zn
#6: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 9 / Source method: obtained synthetically / Formula: C3H8O3
#7: Chemical
ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C2H3O2
#8: Chemical
ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C4H10O3
#9: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 532 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestN

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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: 2.37 Å3/Da / Density % sol: 48.21 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.1 M MES pH6.5, 0.01 M ZnSO4, 25% PEG MME 550, 0.01 M Praseodymium acetate hydrate

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Mar 23, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.9→38.9 Å / Num. obs: 73396 / % possible obs: 99.9 % / Redundancy: 6.7 % / CC1/2: 0.998 / Rmerge(I) obs: 0.122 / Net I/σ(I): 12.9
Reflection shellResolution: 1.9→1.968 Å / Num. unique obs: 7234 / CC1/2: 0.626

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Processing

Software
NameVersionClassification
PHENIXv1.2refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.9→1.968 Å / Cross valid method: FREE R-VALUE
RfactorNum. reflection% reflection
Rfree0.2404 --
Rwork0.1928 --
obs-73390 100 %
Refinement stepCycle: LAST / Resolution: 1.9→1.968 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6797 0 150 532 7479

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