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- EMDB-33883: Structural basis of human PRPS2 filaments -

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Basic information

Entry
Database: EMDB / ID: EMD-33883
TitleStructural basis of human PRPS2 filaments
Map data
Sample
  • Complex: Filament structure of human phosphoribosylpyrophosphate synthetase2.
    • Protein or peptide: Ribose-phosphate pyrophosphokinase 2
  • Ligand: PHOSPHATE IONPhosphate
  • Ligand: MAGNESIUM ION
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
Keywordsphosphoribosylpyrophosphate synthetase / complex / filament / TRANSFERASE
Function / homology
Function and homology information


AMP biosynthetic process / 5-Phosphoribose 1-diphosphate biosynthesis / ribose phosphate diphosphokinase complex / ribose-phosphate diphosphokinase / ribose phosphate diphosphokinase activity / 5-phosphoribose 1-diphosphate biosynthetic process / pentose-phosphate shunt / purine nucleotide biosynthetic process / nucleobase-containing compound metabolic process / AMP binding ...AMP biosynthetic process / 5-Phosphoribose 1-diphosphate biosynthesis / ribose phosphate diphosphokinase complex / ribose-phosphate diphosphokinase / ribose phosphate diphosphokinase activity / 5-phosphoribose 1-diphosphate biosynthetic process / pentose-phosphate shunt / purine nucleotide biosynthetic process / nucleobase-containing compound metabolic process / AMP binding / animal organ regeneration / ADP binding / GDP binding / kinase activity / carbohydrate binding / phosphorylation / magnesium ion binding / protein homodimerization activity / ATP binding / identical protein binding / cytosol / cytoplasm
Similarity search - Function
Phosphoribosyl pyrophosphate synthetase, conserved site / Phosphoribosyl pyrophosphate synthase signature. / Ribose-phosphate pyrophosphokinase, bacterial-type / N-terminal domain of ribose phosphate pyrophosphokinase / Phosphoribosyl synthetase-associated domain / Ribose-phosphate pyrophosphokinase / Ribose-phosphate pyrophosphokinase, N-terminal domain / N-terminal domain of ribose phosphate pyrophosphokinase / Phosphoribosyltransferase-like / Phosphoribosyltransferase domain
Similarity search - Domain/homology
Ribose-phosphate pyrophosphokinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.08 Å
AuthorsLu GM / Hu HH / Liu JL
Funding support China, 2 items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)No. 2021YFA0804700 China
National Natural Science Foundation of China (NSFC)No. 31771490 China
CitationJournal: Cell Biosci / Year: 2023
Title: Structural basis of human PRPS2 filaments.
Authors: Guang-Ming Lu / Huan-Huan Hu / Chia-Chun Chang / Jiale Zhong / Xian Zhou / Chen-Jun Guo / Tianyi Zhang / Yi-Lan Li / Boqi Yin / Ji-Long Liu /
Abstract: BACKGROUND: PRPP synthase (PRPS) transfers the pyrophosphate groups from ATP to ribose-5-phosphate to produce 5-phosphate ribose-1-pyrophosphate (PRPP), a key intermediate in the biosynthesis of ...BACKGROUND: PRPP synthase (PRPS) transfers the pyrophosphate groups from ATP to ribose-5-phosphate to produce 5-phosphate ribose-1-pyrophosphate (PRPP), a key intermediate in the biosynthesis of several metabolites including nucleotides, dinucleotides and some amino acids. There are three PRPS isoforms encoded in human genome. While human PRPS1 (hPRPS1) and human PRPS2 (hPRPS2) are expressed in most tissues, human PRPS3 (hPRPS3) is exclusively expressed in testis. Although hPRPS1 and hPRPS2 share 95% sequence identity, hPRPS2 has been shown to be less sensitive to allosteric inhibition and specifically upregulated in certain cancers in the translational level. Recent studies demonstrate that PRPS can form a subcellular compartment termed the cytoophidium in multiple organisms across prokaryotes and eukaryotes. Forming filaments and cytoophidia is considered as a distinctive mechanism involving the polymerization of the protein. Previously we solved the filament structures of Escherichia coli PRPS (ecPRPS) using cryo-electron microscopy (cryo-EM) .
RESULTS: Order to investigate the function and molecular mechanism of hPRPS2 polymerization, here we solve the polymer structure of hPRPS2 at 3.08 Å resolution. hPRPS2 hexamers stack into polymers ...RESULTS: Order to investigate the function and molecular mechanism of hPRPS2 polymerization, here we solve the polymer structure of hPRPS2 at 3.08 Å resolution. hPRPS2 hexamers stack into polymers in the conditions with the allosteric/competitive inhibitor ADP. The binding modes of ADP at the canonical allosteric site and at the catalytic active site are clearly determined. A point mutation disrupting the inter-hexamer interaction prevents hPRPS2 polymerization and results in significantly reduced catalytic activity.
CONCLUSION: Findings suggest that the regulation of hPRPS2 polymer is distinct from ecPRPS polymer and provide new insights to the regulation of hPRPS2 with structural basis.
History
DepositionJul 21, 2022-
Header (metadata) releaseAug 2, 2023-
Map releaseAug 2, 2023-
UpdateSep 20, 2023-
Current statusSep 20, 2023Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_33883.png

Downloads & links

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Map

FileDownload / File: emd_33883.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.06 Å
Density
Contour LevelBy AUTHOR: 0.05
Minimum - Maximum-0.15039216 - 0.23205559
Average (Standard dev.)0.00020716658 (±0.011308424)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 271.36 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_33883_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_33883_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_33883_half_map_2.map
Projections & Slices
AxesZYX

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Sample components

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Entire : Filament structure of human phosphoribosylpyrophosphate synthetase2.

EntireName: Filament structure of human phosphoribosylpyrophosphate synthetase2.
Components
  • Complex: Filament structure of human phosphoribosylpyrophosphate synthetase2.
    • Protein or peptide: Ribose-phosphate pyrophosphokinase 2
  • Ligand: PHOSPHATE IONPhosphate
  • Ligand: MAGNESIUM ION
  • Ligand: ADENOSINE-5'-DIPHOSPHATE

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Supramolecule #1: Filament structure of human phosphoribosylpyrophosphate synthetase2.

SupramoleculeName: Filament structure of human phosphoribosylpyrophosphate synthetase2.
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Ribose-phosphate pyrophosphokinase 2

MacromoleculeName: Ribose-phosphate pyrophosphokinase 2 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO / EC number: ribose-phosphate diphosphokinase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 35.640969 KDa
Recombinant expressionOrganism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
SequenceString: MPNIVLFSGS SHQDLSQRVA DRLGLELGKV VTKKFSNQET SVEIGESVRG EDVYIIQSGC GEINDNLMEL LIMINACKIA SSSRVTAVI PCFPYARQDK KDKSRAPISA KLVANMLSVA GADHIITMDL HASQIQGFFD IPVDNLYAEP AVLQWIRENI A EWKNCIIV ...String:
MPNIVLFSGS SHQDLSQRVA DRLGLELGKV VTKKFSNQET SVEIGESVRG EDVYIIQSGC GEINDNLMEL LIMINACKIA SSSRVTAVI PCFPYARQDK KDKSRAPISA KLVANMLSVA GADHIITMDL HASQIQGFFD IPVDNLYAEP AVLQWIRENI A EWKNCIIV SPDAGGAKRV TSIADRLNVE FALIHKERKK ANEVDRMVLV GDVKDRVAIL VDDMADTCGT ICHAADKLLS AG ATKVYAI LTHGIFSGPA ISRINNAAFE AVVVTNTIPQ EDKMKHCTKI QVIDISMILA EAIRRTHNGE SVSYLFSHVP LHH HHHH

UniProtKB: Ribose-phosphate pyrophosphokinase 2

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Macromolecule #2: PHOSPHATE ION

MacromoleculeName: PHOSPHATE ION / type: ligand / ID: 2 / Number of copies: 6 / Formula: PO4
Molecular weightTheoretical: 94.971 Da
Chemical component information

ChemComp-PO4:
PHOSPHATE ION / Phosphate

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Macromolecule #3: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 6 / Formula: MG
Molecular weightTheoretical: 24.305 Da

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Macromolecule #4: ADENOSINE-5'-DIPHOSPHATE

MacromoleculeName: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 12 / Formula: ADP
Molecular weightTheoretical: 427.201 Da
Chemical component information

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation statefilament

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Sample preparation

BufferpH: 7.5
Component:
ConcentrationFormulaName
150.0 mMNaClSodium chloridesodium chloride
2.0 mMADPAdenosine diphosphate
10.0 mMMgCl2Magnesium chloride
25.0 mMTris-HClTrisTrimethylol aminomethane hydrochloride
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Support film - Material: GOLD
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K

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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 / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 22500
Sample stageCooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 2403 / Average exposure time: 4.0 sec. / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 681672
Startup modelType of model: OTHER
Initial angle assignmentType: NOT APPLICABLE
Final 3D classificationNumber classes: 8
Final angle assignmentType: NOT APPLICABLE
Final reconstructionNumber classes used: 1 / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.08 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 140303
FSC plot (resolution estimation)

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