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- EMDB-63239: Munc13-4-Rab27a complex consensus map -

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Basic information

Entry
Database: EMDB / ID: EMD-63239
TitleMunc13-4-Rab27a complex consensus map
Map data
Sample
  • Complex: Munc13-4-Rab27a complex with GppNHp
KeywordsVesicle tethering / Familial hemophagocytic lymphohistiocytosis type 3 /FHL3 / Griscelli syndrome type 2 /GS2 / EXOCYTOSIS
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.42 Å
AuthorsZheng X / Liu CQ / Wang S / Guan JL / He J / Ma C
Funding support China, 6 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32225024, 92254302 China
National Natural Science Foundation of China (NSFC)2022YFA1206001 China
National Natural Science Foundation of China (NSFC)32241021 China
National Natural Science Foundation of China (NSFC)32170189 China
National Natural Science Foundation of China (NSFC)3231163669 China
Other private2024A04J6348
CitationJournal: Nat Commun / Year: 2025
Title: Munc13-4 mediates tumor immune evasion by regulating the sorting and secretion of PD-L1 via exosomes.
Authors: Chuqi Liu / Dexiang Liu / Xiang Zheng / Jiali Guan / Xinyan Zhou / Haikun Zhang / Shen Wang / Qiubai Li / Gan Lu / Jun He / Cong Ma /
Abstract: Tumor-derived exosomes carry programmed death-ligand 1 (PD-L1), which binds programmed cell death protein 1 (PD-1) on T cells, suppressing immune responses locally and systemically. However, the ...Tumor-derived exosomes carry programmed death-ligand 1 (PD-L1), which binds programmed cell death protein 1 (PD-1) on T cells, suppressing immune responses locally and systemically. However, the mechanisms governing exosomal PD-L1 sorting and secretion remain elusive. Here, we identify Munc13-4 as a crucial regulator of this process. Deletion of Munc13-4 in breast tumors enhances T cell-mediated anti-tumor immunity, suppresses tumor growth, and improves the efficacy of immune checkpoint inhibitors. Mechanistically, Munc13-4 collaborates with hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), Rab27, and SNAREs to facilitate PD-L1 sorting and secretion via exosomes. Cryogenic electron microscopy (cryo-EM) analysis of the Munc13-4-Rab27a complex provide structural insights into exosome secretion. Importantly, PD-L1 sorting relies on a ternary complex composed of Munc13-4, PD-L1 and HRS, which is regulated by interferon gamma (IFNγ) signaling. A designed peptide that disrupts Munc13-4-PD-L1 interaction impedes PD-L1 sorting, enhances antitumor immunity, and suppresses tumor growth, highlighting the therapeutic potential of targeting this pathway.
History
DepositionJan 21, 2025-
Header (metadata) releaseDec 3, 2025-
Map releaseDec 3, 2025-
UpdateDec 3, 2025-
Current statusDec 3, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_63239.png

Downloads & links

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Map

FileDownload / File: emd_63239.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 600 pix.
= 438. Å		0.73 Å/pix.
x 600 pix.
= 438. Å		0.73 Å/pix.
x 600 pix.
= 438. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.73 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.4615197 - 0.78663826
Average (Standard dev.)-0.000057332523 (±0.00699085)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions600600600
Spacing600600600
CellA=B=C: 438.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_63239_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_63239_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Munc13-4-Rab27a complex with GppNHp

EntireName: Munc13-4-Rab27a complex with GppNHp
Components
  • Complex: Munc13-4-Rab27a complex with GppNHp

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Supramolecule #1: Munc13-4-Rab27a complex with GppNHp

SupramoleculeName: Munc13-4-Rab27a complex with GppNHp / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)

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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: 8.2
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK II

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.42 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 102381
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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