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- PDB-6z0h: Structure of TREM2 transmembrane helix K186A variant in DPC micelles -

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Basic information

Entry
Database: PDB / ID: 6z0h
TitleStructure of TREM2 transmembrane helix K186A variant in DPC micelles
ComponentsTriggering receptor expressed on myeloid cells 2
KeywordsMEMBRANE PROTEIN / neurodegeneration / proteolysis
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
Triggering receptor expressed on myeloid cells 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / simulated annealing
AuthorsSteiner, A. / Schlepkow, K. / Brunner, B. / Steiner, H. / Haass, C. / Hagn, F.
Funding support Germany, European Union, 2items
OrganizationGrant numberCountry
Helmholtz AssociationVG-NG-1039 Germany
European Communitys Seventh Framework Programme291763European Union
CitationJournal: Embo J. / Year: 2020
Title: gamma-Secretase cleavage of the Alzheimer risk factor TREM2 is determined by its intrinsic structural dynamics.
Authors: Steiner, A. / Schlepckow, K. / Brunner, B. / Steiner, H. / Haass, C. / Hagn, F.
History
DepositionMay 8, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 16, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 28, 2020Group: Database references / Category: citation / Item: _citation.journal_volume
Revision 1.2Jun 14, 2023Group: Database references / Other / Category: database_2 / pdbx_database_status
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_nmr_data
Revision 1.3Jun 19, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 / Item: _database_2.pdbx_DOI

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Triggering receptor expressed on myeloid cells 2


Theoretical massNumber of molelcules
Total (without water)5,1141
Polymers5,1141
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area0 Å2
ΔGint0 kcal/mol
Surface area4870 Å2
MethodPISA
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)20 / 100structures with the lowest energy
RepresentativeModel #1lowest energy

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Components

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


Mass: 5114.018 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TREM2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9NZC2

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDSample stateSpectrometer-IDType
111isotropic12D HSQC
121isotropic13D HNCO
131isotropic13D HNCA
141isotropic13D HN(CA)CB
151isotropic13D HN(CO)CA
171isotropic23D 1H-15N NOESY

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Sample preparation

DetailsType: micelle
Contents: 500 uM U-2H,U-13C,U-15N TREM2 transmembrane helix in DPC micelles, 95% H2O/5% D2O
Details: 2H,13C,15N-labeled TREM2-TMH in DPC micelles / Label: 2H,13C,15N_sample / Solvent system: 95% H2O/5% D2O
SampleConc.: 500 uM / Component: TREM2 transmembrane helix in DPC micelles / Isotopic labeling: U-2H,U-13C,U-15N
Sample conditionsIonic strength: 100 mM / Label: conditions_1 / pH: 7.0 / Pressure: 1 atm / Temperature: 310 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker AVANCE IIIBrukerAVANCE III6001
Bruker AVANCE IIIBrukerAVANCE III9502

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Processing

NMR software
NameDeveloperClassification
TopSpinBruker Biospincollection
TopSpinBruker Biospinprocessing
SparkyGoddardchemical shift assignment
SparkyGoddardpeak picking
X-PLOR NIHSchwieters, Kuszewski, Tjandra and Clorestructure calculation
X-PLOR NIHSchwieters, Kuszewski, Tjandra and Clorerefinement
RefinementMethod: simulated annealing / Software ordinal: 6
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 100 / Conformers submitted total number: 20

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