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- PDB-5eli: Triggering receptor expressed on myeloid cells 2 -

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Basic information

Entry
Database: PDB / ID: 5eli
TitleTriggering receptor expressed on myeloid cells 2
ComponentsTriggering receptor expressed on myeloid cells 2
KeywordsIMMUNE SYSTEM / Activating receptors / TREM2 / innate immunity / immune system receptor
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 / Immunoglobulins / Immunoglobulin-like fold / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
Triggering receptor expressed on myeloid cells 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.0977 Å
AuthorsBrett, T.J. / Kober, D.L.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)R01-HL119813 United States
CitationJournal: Elife / Year: 2016
Title: Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms.
Authors: Kober, D.L. / Alexander-Brett, J.M. / Karch, C.M. / Cruchaga, C. / Colonna, M. / Holtzman, M.J. / Brett, T.J.
History
DepositionNov 4, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 28, 2016Provider: repository / Type: Initial release
Revision 1.1Jan 4, 2017Group: Database references
Revision 1.2Sep 6, 2017Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Nov 1, 2017Group: Author supporting evidence / Category: pdbx_struct_assembly_auth_evidence
Revision 1.4Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.5Jul 29, 2020Group: Data collection / Derived calculations / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_chem_comp_identifier / pdbx_entity_nonpoly / struct_conn / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _struct_conn.pdbx_role
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.6Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Triggering receptor expressed on myeloid cells 2
B: Triggering receptor expressed on myeloid cells 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,7404
Polymers28,2982
Non-polymers4422
Water00
1
A: Triggering receptor expressed on myeloid cells 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)14,3702
Polymers14,1491
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Triggering receptor expressed on myeloid cells 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)14,3702
Polymers14,1491
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)125.763, 125.763, 183.659
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number181
Space group name H-MP6422
DetailsMonomer confirmed by size exclusion chromatography

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Components

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


Mass: 14148.990 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TREM2 / Plasmid: pHLSEC / Cell (production host): epithelial / Cell line (production host): HEK293F / Organ (production host): kidney / Production host: Homo sapiens (human) / Tissue (production host): embryonic kidney / References: UniProt: Q9NZC2
#2: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION

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Sample preparation

CrystalDensity Matthews: 7.41 Å3/Da / Density % sol: 85.23 %
Crystal growTemperature: 290 K / Method: vapor diffusion, hanging drop / pH: 7.1
Details: 2 M NaCl, 0.2 M MgCl2, 0.2 M NDSB 201, 100 mM HEPES pH 7.1

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97918 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 1, 2012
RadiationMonochromator: ROSENBAUM-ROCK HIGH-RESOLUTION DOUBLE CRYSTAL SI(111)
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 3.0977→50 Å / Num. all: 16285 / Num. obs: 16285 / % possible obs: 99.9 % / Observed criterion σ(I): 0 / Redundancy: 12.9 % / Biso Wilson estimate: 86.38 Å2 / Rmerge(I) obs: 0.109 / Rsym value: 0.109 / Net I/σ(I): 20.96
Reflection shellResolution: 3.0977→3.21 Å / Redundancy: 13.4 % / Rmerge(I) obs: 0.8 / Mean I/σ(I) obs: 1.72 / % possible all: 100

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Processing

Software
NameVersionClassification
PHENIX(1.10_2155: ???)refinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1U9K

1u9k


Resolution: 3.0977→40.689 Å / SU ML: 0.48 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 29.69 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2736 807 4.99 %Random selection
Rwork0.2605 ---
obs0.2611 16171 99.61 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 85.86 Å2
Refinement stepCycle: LAST / Resolution: 3.0977→40.689 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1784 0 0 0 1784
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0061826
X-RAY DIFFRACTIONf_angle_d1.1812484
X-RAY DIFFRACTIONf_dihedral_angle_d14.6391076
X-RAY DIFFRACTIONf_chiral_restr0.059284
X-RAY DIFFRACTIONf_plane_restr0.004314
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.0977-3.29170.40591310.37452482X-RAY DIFFRACTION100
3.2917-3.54580.34511300.30732505X-RAY DIFFRACTION100
3.5458-3.90230.27751320.29522529X-RAY DIFFRACTION100
3.9023-4.46640.26551340.25822532X-RAY DIFFRACTION100
4.4664-5.62480.21711350.21952576X-RAY DIFFRACTION100
5.6248-40.69210.26591450.24222740X-RAY DIFFRACTION99
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)
14.34763.03784.81634.6598-0.3682.0694-0.06290.9989-0.103-0.97280.3946-1.3782-0.9191.7022-0.3540.94750.05830.25371.13750.11690.8778-42.627314.2105-20.4624
29.1589-1.0821.83836.9655-0.73749.45320.6773-0.14670.9355-0.5209-0.2297-0.3936-1.39440.81160.18061.1101-0.15610.03170.50070.0190.7011-51.599517.4805-6.1158
32.0012-2.71444.14811.0513-0.17258.7695-1.082.0792.7319-0.4493-0.4643-0.75161.98792.18281.74261.4628-0.10270.41371.59220.47272.0853-49.515132.9817-19.1605
45.55212.8751-1.79845.4004-0.29432.08780.21350.34951.11710.3103-0.14560.4974-1.4646-0.54180.02611.15440.0660.07030.48880.0950.6706-59.127913.0733-9.9706
55.79042.0204-0.98875.43823.45193.42020.17770.38890.2857-0.5002-0.6018-0.4902-0.21190.20390.09810.95160.05660.09270.50890.11020.4984-53.216910.6045-13.8902
64.09611.90280.43622.94721.07932.82120.43020.61060.8909-1.79990.14770.1832-1.68380.7318-0.5621.5716-0.02580.23070.94170.23360.8093-51.387819.4832-19.2155
73.16382.25513.37028.06542.42433.49420.77880.86930.7364-0.64470.3578-1.1224-1.58660.8421-0.96121.0755-0.22270.20941.21220.18490.7196-44.977520.1225-18.3546
86.2477-2.0708-2.42281.99884.7827.05030.4808-0.0610.58371.45490.5584-1.14991.89413.1512-1.07791.04450.2492-0.07011.5618-0.50651.0705-67.622627.0636-25.7941
91.2475-0.53941.91787.9369-6.00087.50540.14050.1986-0.1056-0.0562-0.2271-0.4740.14710.36580.07461.01150.3919-0.02930.705-0.00380.5905-70.130512.0165-19.1175
107.4178-1.9208-0.53588.4268-4.914.24060.70750.18040.5831-0.4578-0.72041.7613-1.1861-1.3855-0.13671.19850.4554-0.19151.1618-0.08780.7557-81.044315.4114-23.5929
119.5806-2.21371.48728.09582.05641.30020.2577-0.31-0.0597-0.59580.1469-0.31321.07520.6112-0.75431.08620.1413-0.25950.5668-0.07510.5581-71.28891.0002-22.9352
123.3239-0.1985-0.39624.3855-3.20855.18370.70221.1021-0.0745-1.2966-0.30860.29250.5652-0.5094-0.19371.41230.5258-0.08671.0073-0.00360.5878-71.501612.8413-29.5424
133.4944-0.19930.11064.2529-2.87895.10120.31080.45780.4419-0.0451-0.20180.3405-0.4349-1.4223-0.63381.19920.3527-0.0720.75360.06450.6933-79.600715.9003-19.5743
143.469-0.68530.9235.32684.12596.02990.675-0.2819-0.20311.083-0.3148-0.7181-2.54530.0768-0.02731.33790.4902-0.15170.7668-0.04480.6597-73.505322.4653-24.6848
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 20 through 37 )
2X-RAY DIFFRACTION2chain 'A' and (resid 38 through 53 )
3X-RAY DIFFRACTION3chain 'A' and (resid 54 through 59 )
4X-RAY DIFFRACTION4chain 'A' and (resid 60 through 76 )
5X-RAY DIFFRACTION5chain 'A' and (resid 77 through 97 )
6X-RAY DIFFRACTION6chain 'A' and (resid 98 through 116 )
7X-RAY DIFFRACTION7chain 'A' and (resid 117 through 131 )
8X-RAY DIFFRACTION8chain 'B' and (resid 20 through 27 )
9X-RAY DIFFRACTION9chain 'B' and (resid 28 through 47 )
10X-RAY DIFFRACTION10chain 'B' and (resid 48 through 69 )
11X-RAY DIFFRACTION11chain 'B' and (resid 70 through 76 )
12X-RAY DIFFRACTION12chain 'B' and (resid 77 through 105 )
13X-RAY DIFFRACTION13chain 'B' and (resid 106 through 116 )
14X-RAY DIFFRACTION14chain 'B' and (resid 117 through 131 )

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