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EndoMAP.v1, a Structural Protein Complex Landscape of Human Endosomes
Miguel A Gonzalez-Lozano1,2, Ernst W Schmid3, Enya Miguel Whelan1,2
1Department of Cell Biology, Harvard Medical School, Boston MA, USA.
Biorxiv : the Preprint Server for Biology
|February 20, 2025
Summary
Researchers mapped the human endosomal structural interactome using mass spectrometry and AlphaFold. This reveals new protein complexes, including TMEM230 and TMEM9/9B, crucial for organelle function and protein sorting.
Area of Science:
- Cell Biology
- Structural Biology
- Proteomics
Background:
- Early/sorting endosomes manage cellular proteomes by sorting plasma membrane proteins for recycling or lysosomal degradation.
- Understanding the molecular machinery of endosome maturation requires identifying protein interactions and assembly dynamics.
- Many endosomal protein interactions and complex structures remain uncharacterized.
Purpose of the Study:
- To systematically map the human endosomal structural interactome.
- To generate structural models of endosomal protein complexes using integrated experimental and computational approaches.
- To validate predicted protein complexes in a cellular context.
Main Methods:
- Purified early endosomes were analyzed using cross-linking and native gel mass spectrometry.
- AlphaFold and computational methods were employed to predict protein structures and interactions.
- Candidate complexes were validated in induced neurons.
Main Results:
- A systematic human endosomal structural interactome was created, presenting numerous structural models for protein pairs and assemblies.
- Experimental cross-links from native endosomes support the predicted structures.
- Two novel complexes were validated: TMEM230 with ATP8/11 lipid flippases and TMEM9/9B with CLCN3/4/5 chloride-proton antiporters.
Conclusions:
- The study provides a comprehensive structural interactome of human endosomes.
- The findings offer insights into the structural mechanisms of endosomal protein regulation.
- This resource facilitates further investigation into organellar structural interactomes and validation of structural predictions.
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