EndoMAP.v1

EndoMAP.v1 charts the structural landscape of human early endosome complexes by combining crosslinking and native gel mass spectrometry with AlphaFold predictions and computational analysis to create a systematic human endosomal structural interactome.

Key Features:

• Structural models: Provides 229 structural models for endosomal protein pairs and additional higher-order assemblies supported by experimental crosslinks from their native subcellular context.
• Structural network viewer: Offers an accompanying structural network viewer for exploring the endosomal structural interactome.
• Experimental validation framework: Supports large-scale validation of structural predictions through experimental crosslink data from purified early endosomes.

Scientific Applications:

• Organelle structural interactome analysis: Provides an experimental framework for understanding organellar structural interactomes and their molecular organization.
• Candidate complex validation: Enables validation of candidate protein complexes, as demonstrated for TMEM230 as a subunit of ATP8 and ATP11 lipid flippases and TMEM9 and TMEM9B as subunits of CLCN3, CLCN4 and CLCN5 chloride-proton antiporters.
• Regulatory mechanism investigation: Suggests structural mechanisms for previously reported regulatory processes in endosome maturation and proteome control.

Methodology:

Crosslinking and native gel mass spectrometry of purified early endosomes combined with AlphaFold predictions and computational analysis.