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- EMDB-33632: ApoSIDT2-pH7.4 -

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ID or keywords:

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Basic information

Entry
Database: EMDB / ID: EMD-33632
TitleApoSIDT2-pH7.4
Map data
Sample
  • Organelle or cellular component: dimer of SIDT2
    • Protein or peptide: SID1 transmembrane family member 2
  • Ligand: ZINC ION
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsmembrane protein
Function / homology
Function and homology information


nucleic acid transmembrane transporter activity / AP-1 adaptor complex binding / RNA transmembrane transporter activity / RNA transport / AP-2 adaptor complex binding / type B pancreatic cell development / regulation of insulin secretion involved in cellular response to glucose stimulus / type B pancreatic cell proliferation / RNA catabolic process / response to glucose ...nucleic acid transmembrane transporter activity / AP-1 adaptor complex binding / RNA transmembrane transporter activity / RNA transport / AP-2 adaptor complex binding / type B pancreatic cell development / regulation of insulin secretion involved in cellular response to glucose stimulus / type B pancreatic cell proliferation / RNA catabolic process / response to glucose / cell morphogenesis / glucose homeostasis / double-stranded RNA binding / lysosome / lysosomal membrane / DNA binding / plasma membrane
Similarity search - Function
SID1 transmembrane family / dsRNA-gated channel SID-1
Similarity search - Domain/homology
SID1 transmembrane family member 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.16 Å
AuthorsGong DS
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2023
Title: Structural insight into the human SID1 transmembrane family member 2 reveals its lipid hydrolytic activity.
Authors: Dandan Qian / Ye Cong / Runhao Wang / Quan Chen / Chuangye Yan / Deshun Gong /
Abstract: The systemic RNAi-defective (SID) transmembrane family member 2 (SIDT2) is a putative nucleic acid channel or transporter that plays essential roles in nucleic acid transport and lipid metabolism. ...The systemic RNAi-defective (SID) transmembrane family member 2 (SIDT2) is a putative nucleic acid channel or transporter that plays essential roles in nucleic acid transport and lipid metabolism. Here, we report the cryo-electron microscopy (EM) structures of human SIDT2, which forms a tightly packed dimer with extensive interactions mediated by two previously uncharacterized extracellular/luminal β-strand-rich domains and the unique transmembrane domain (TMD). The TMD of each SIDT2 protomer contains eleven transmembrane helices (TMs), and no discernible nucleic acid conduction pathway has been identified within the TMD, suggesting that it may act as a transporter. Intriguingly, TM3-6 and TM9-11 form a large cavity with a putative catalytic zinc atom coordinated by three conserved histidine residues and one aspartate residue lying approximately 6 Å from the extracellular/luminal surface of the membrane. Notably, SIDT2 can hydrolyze C18 ceramide into sphingosine and fatty acid with a slow rate. The information presented advances the understanding of the structure-function relationships in the SID1 family proteins.
History
DepositionJun 18, 2022-
Header (metadata) releaseJun 21, 2023-
Map releaseJun 21, 2023-
UpdateNov 29, 2023-
Current statusNov 29, 2023Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_33632.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.0979 Å
Density
Contour LevelBy AUTHOR: 0.38
Minimum - Maximum-1.5747001 - 2.6994948
Average (Standard dev.)0.0009802263 (±0.060944717)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 281.0624 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_33632_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_33632_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : dimer of SIDT2

EntireName: dimer of SIDT2
Components
  • Organelle or cellular component: dimer of SIDT2
    • Protein or peptide: SID1 transmembrane family member 2
  • Ligand: ZINC ION
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: dimer of SIDT2

SupramoleculeName: dimer of SIDT2 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: SID1 transmembrane family member 2

MacromoleculeName: SID1 transmembrane family member 2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 94.539938 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MFALGLPFLV LLVASVESHL GVLGPKNVSQ KDAEFERTYV DEVNSELVNI YTFNHTVTRN RTEGVRVSVN VLNKQKGAPL LFVVRQKEA VVSFQVPLIL RGMFQRKYLY QKVERTLCQP PTKNESEIQF FYVDVSTLSP VNTTYQLRVS RMDDFVLRTG E QFSFNTTA ...String:
MFALGLPFLV LLVASVESHL GVLGPKNVSQ KDAEFERTYV DEVNSELVNI YTFNHTVTRN RTEGVRVSVN VLNKQKGAPL LFVVRQKEA VVSFQVPLIL RGMFQRKYLY QKVERTLCQP PTKNESEIQF FYVDVSTLSP VNTTYQLRVS RMDDFVLRTG E QFSFNTTA AQPQYFKYEF PEGVDSVIVK VTSNKAFPCS VISIQDVLCP VYDLDNNVAF IGMYQTMTKK AAITVQRKDF PS NSFYVVV VVKTEDQACG GSLPFYPFAE DEPVDQGHRQ KTLSVLVSQA VTSEAYVSGM LFCLGIFLSF YLLTVLLACW ENW RQKKKT LLVAIDRACP ESGHPRVLAD SFPGSSPYEG YNYGSFENVS GSTDGLVDSA GTGDLSYGYQ GRSFEPVGTR PRVD SMSSV EEDDYDTLTD IDSDKNVIRT KQYLYVADLA RKDKRVLRKK YQIYFWNIAT IAVFYALPVV QLVITYQTVV NVTGN QDIC YYNFLCAHPL GNLSAFNNIL SNLGYILLGL LFLLIILQRE INHNRALLRN DLCALECGIP KHFGLFYAMG TALMME GLL SACYHVCPNY TNFQFDTSFM YMIAGLCMLK LYQKRHPDIN ASAYSAYACL AIVIFFSVLG VVFGKGNTAF WIVFSII HI IATLLLSTQL YYMGRWKLDS GIFRRILHVL YTDCIRQCSG PLYVDRMVLL VMGNVINWSL AAYGLIMRPN DFASYLLA I GICNLLLYFA FYIIMKLRSG ERIKLIPLLC IVCTSVVWGF ALFFFFQGLS TWQKTPAESR EHNRDCILLD FFDDHDIWH FLSSIAMFGS FLVLLTLDDD LDTVQRDKIY VF

UniProtKB: SID1 transmembrane family member 2

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Macromolecule #3: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

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Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 6 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.3 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER / Details: AlphaFold
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.16 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 183937
FSC plot (resolution estimation)

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