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- EMDB-42345: Structural Basis of Human NOX5 Activation -

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Basic information

Entry
Database: EMDB / ID: EMD-42345
TitleStructural Basis of Human NOX5 Activation
Map data
Sample
  • Complex: NADPH oxidase 5
    • Protein or peptide: NADPH oxidase 5 (NOX5)
Keywordsenzyme / oxidase / activation mechanism / MEMBRANE PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.32 Å
AuthorsCui C / Jiang M / Sun J
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM141357 United States
CitationJournal: Nat Commun / Year: 2024
Title: Structural basis of human NOX5 activation.
Authors: Chenxi Cui / Meiqin Jiang / Nikhil Jain / Sourav Das / Yu-Hua Lo / Ali A Kermani / Tanadet Pipatpolkai / Ji Sun /
Abstract: NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, ...NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular diseases. NOX5 is activated by intracellular calcium signaling, but the underlying molecular mechanism of which - in particular, how calcium triggers electron transfer from NADPH to FAD - is still unclear. Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogenic electron microscopy (cryo-EM). By combining biochemistry, mutagenesis analyses, and molecular dynamics (MD) simulations, we decode the molecular basis of NOX5 activation and electron transfer. We find that calcium binding to the EF-hand domain increases NADPH dynamics, permitting electron transfer between NADPH and FAD and superoxide production. Our structural findings also uncover a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulation mechanisms of reactive oxygen species (ROS) production.
History
DepositionOct 12, 2023-
Header (metadata) releaseMay 1, 2024-
Map releaseMay 1, 2024-
UpdateMar 26, 2025-
Current statusMar 26, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_42345.png

Downloads & links

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Map

FileDownload / File: emd_42345.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.3 Å/pix.
x 224 pix.
= 290.528 Å		1.3 Å/pix.
x 224 pix.
= 290.528 Å		1.3 Å/pix.
x 224 pix.
= 290.528 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.297 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.9
Minimum - Maximum-1.4606209 - 3.6737347
Average (Standard dev.)0.0050290227 (±0.06966043)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions224224224
Spacing224224224
CellA=B=C: 290.528 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_42345_half_map_1.map
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Half map: #2

Fileemd_42345_half_map_2.map
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Sample components

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Entire : NADPH oxidase 5

EntireName: NADPH oxidase 5
Components
  • Complex: NADPH oxidase 5
    • Protein or peptide: NADPH oxidase 5 (NOX5)

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Supramolecule #1: NADPH oxidase 5

SupramoleculeName: NADPH oxidase 5 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: NADPH oxidase 5 (NOX5)

MacromoleculeName: NADPH oxidase 5 (NOX5) / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
SequenceString: MSAEEDARWL RWVTQQFKTI AGEDGEISLQ EFKAALHVKE SFFAERFFAL FDSDRSGTIT LQELQEALTL LIHGSPMDKL KFLFQVYDID GSGSIDPDEL RTVLQSCLRE SAISLPDEKL DQLTLALFES ADADGNGAIT FEELRDELQR FPGVMENLTI SAAHWLTAPA ...String:
MSAEEDARWL RWVTQQFKTI AGEDGEISLQ EFKAALHVKE SFFAERFFAL FDSDRSGTIT LQELQEALTL LIHGSPMDKL KFLFQVYDID GSGSIDPDEL RTVLQSCLRE SAISLPDEKL DQLTLALFES ADADGNGAIT FEELRDELQR FPGVMENLTI SAAHWLTAPA PRPRPRRPRQ LTRAYWHNHR SQLFCLATYA GLHVLLFGLA ASAHRDLGAS VMVAKGCGQC LNFDCSFIAV LMLRRCLTWL RATWLAQVLP LDQNIQFHQL MGYVVVGLSL VHTVAHTVNF VLQAQAEASP FQFWELLLTT RPGIGWVHGS ASPTGVALLL LLLLMFICSS SCIRRSGHFE VFYWTHLSYL LVWLLLIFHG PNFWKWLLVP GILFFLEKAI GLAVSRMAAV CIMEVNLLPS KVTHLLIKRP PFFHYRPGDY LYLNIPTIAR YEWHPFTISS APEQKDTIWL HIRSQGQWTN RLYESFKASD PLGRGSKRLS RSVTMRKSQR SSKGSEILLE KHKFCNIKCY IDGPYGTPTR RIFASEHAVL IGAGIGITPF ASILQSIMYR HQKRKHTCPS CQHSWIEGVQ DNMKLHKVDF IWINRDQRSF EWFVSLLTKL EMDQAEEAQY GRFLELHMYM TSALGKNDMK AIGLQMALDL LANKEKKDSI TGLQTRTQPG RPDWSKVFQK VAAEKKGKVQ VFFCGSPALA KVLKGHCEKF GFRFFQENF

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.32 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 220000
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: ANGULAR RECONSTITUTION

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