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- EMDB-52203: Cryo-EM structure of CD36 protein complex with Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-52203
TitleCryo-EM structure of CD36 protein complex with Fab
Map data
Sample
  • Complex: Extracellular domain of CD36; Fab of PLT012
KeywordsCD36 / Fab / fatty acid uptake / TRANSPORT PROTEIN
Biological speciesCricetulus griseus (Chinese hamster)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.32 Å
AuthorsNazarov S / Yu YR
Funding support Switzerland, 1 items
OrganizationGrant numberCountry
Swiss National Science Foundation Switzerland
CitationJournal: Cancer Discov / Year: 2025
Title: PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Antitumor Immunity Against Liver Cancer and Liver Metastasis.
Authors: Sheue-Fen Tzeng / Yi-Ru Yu / Jaeoh Park / Janusz von Renesse / Huey-Wen Hsiao / Chen-Hsuan Hsu / Josep Garnica / Jintian Chen / Lu-Ting Chiu / Jonas Santol / Tse-Yu Chen / Pei-Han Chung / ...Authors: Sheue-Fen Tzeng / Yi-Ru Yu / Jaeoh Park / Janusz von Renesse / Huey-Wen Hsiao / Chen-Hsuan Hsu / Josep Garnica / Jintian Chen / Lu-Ting Chiu / Jonas Santol / Tse-Yu Chen / Pei-Han Chung / Lana E Kandalaft / Patrick Starlinger / Rodney Cheng-En Hsieh / Ming-Chin Yu / Pei-Wen Hsiao / Santiago J Carmona / Hung-Kai Chen / Zhen Meng / Yun-Han Lin / Jingying Zhou / Chin-Hsien Tsai / Ping-Chih Ho /
Abstract: Tumor cells develop various strategies to evade immune surveillance, one of which involves altering the metabolic state of the tumor microenvironment. In response to metabolic stress in the tumor ...Tumor cells develop various strategies to evade immune surveillance, one of which involves altering the metabolic state of the tumor microenvironment. In response to metabolic stress in the tumor microenvironment, several tumor-infiltrating immune subsets upregulate CD36 to take up lipids. This leads to impaired antitumor immunity, as intratumoral regulatory T cells exhibit increased survival and suppressive activity, whereas CD8+ T cells become more susceptible to ferroptosis and exhaustion. In this study, we develop a humanized anti-CD36 IgG4 antibody, PLT012, against the lipid-binding domain of CD36 with excellent safety and favorable pharmacokinetic features in mice and cynomolgus monkeys. PLT012 alone or in combination with PD-L1 blockade or standard-of-care immunotherapy results in robust antitumor immunity in both immunotherapy-sensitive and -resistant hepatocellular carcinomas (HCC). Notably, PLT012 also reprograms the immune landscape of human HCC ex vivo. Our findings provide proof-of-concept evidence that PLT012 reprograms antitumor immunity in HCC, positioning it as a first-in-class immunotherapy targeting CD36.
SIGNIFICANCE: Despite the success of cancer immunotherapies, like immune checkpoint inhibitors, many patients still fail to demonstrate significant responses because of metabolic constraints in ...SIGNIFICANCE: Despite the success of cancer immunotherapies, like immune checkpoint inhibitors, many patients still fail to demonstrate significant responses because of metabolic constraints in tumors. PLT012 rejuvenates antitumor immunity by targeting metabolic pathways to reprogram the immune landscape of liver cancer and liver metastasis, with potential to influence future HCC immunotherapy.
History
DepositionNov 27, 2024-
Header (metadata) releaseApr 23, 2025-
Map releaseApr 23, 2025-
UpdateAug 13, 2025-
Current statusAug 13, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_52203.png

Downloads & links

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Map

FileDownload / File: emd_52203.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 288 pix.
= 239.04 Å		0.83 Å/pix.
x 288 pix.
= 239.04 Å		0.83 Å/pix.
x 288 pix.
= 239.04 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.08
Minimum - Maximum-0.3331224 - 0.5585012
Average (Standard dev.)0.000021804375 (±0.010778293)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 239.04 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_52203_msk_1.map
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Additional map: Cryo-EM density maps enhanced using EMReady, a three-dimensional...

Fileemd_52203_additional_1.map
AnnotationCryo-EM density maps enhanced using EMReady, a three-dimensional Swin-Conv-UNet-based deep learning framework
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Additional map: Cryo-EM density maps enhanced using cryoTEN, a three-dimensional...

Fileemd_52203_additional_2.map
AnnotationCryo-EM density maps enhanced using cryoTEN, a three-dimensional U-Net style transformer
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Half map: #2

Fileemd_52203_half_map_1.map
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Half map: #1

Fileemd_52203_half_map_2.map
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Sample components

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Entire : Extracellular domain of CD36; Fab of PLT012

EntireName: Extracellular domain of CD36; Fab of PLT012
Components
  • Complex: Extracellular domain of CD36; Fab of PLT012

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Supramolecule #1: Extracellular domain of CD36; Fab of PLT012

SupramoleculeName: Extracellular domain of CD36; Fab of PLT012 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Cricetulus griseus (Chinese hamster)
Molecular weightTheoretical: 105 KDa

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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

Concentration1 mg/mL
BufferpH: 7.5
GridModel: SPT Labtech self-wicking R1.2/0.8 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 283 K / Details: Chameleon system (SPT Labtech).

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Electron microscopy

MicroscopeTFS KRIOS
DetailsCold-FEG fringe-free, AFIS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number real images: 37188 / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 23023142
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 46044
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT

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