Stitching the synapse: cross-linking mass spectrometry into resolving synaptic protein interactions

Proteome-wide chemical cross-linking combined with mass spectrometry (XL-MS) is an untargeted large-scale approach to capture protein structures and interactions in a physiologically relevant context. By applying XL-MS to synaptosome and microsome fractions purified from hippocampus and cerebellum of mouse brain, we generated a protein interaction resource from the 11,999 cross-links identified. Proteins in close proximity are connected by cross-linking reagents in their subcellular compartments in order to reveal potential protein-binding interfaces and novel partnerships (by inter-protein cross-links) as well as elucidate protein conformations (by intra-protein cross-links). This website works best with the Google Chrome or Firefox browser, Internet Explorer is not supported.

Gonzalez-Lozano, M.A. et al. Stitching the synapse: cross-linking mass spectrometry into resolving synaptic protein interactions. Sci Adv. 2020 Feb 19;6(8) PMID: 32128395

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Red node indicates the selected protein
 
Black border indicates presence of
intraprotein cross-links
Edges indicate interprotein cross-links
Edges are color-coded based on individual
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Additional information and a tutorial
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Reference for use of the data

When using the synapse cross-linking data please cite: Gonzalez-Lozano, M.A. et al. Stitching the synapse: cross-linking mass spectrometry into resolving synaptic protein interactions. Sci Adv. 2020 Feb 19;6(8) PMID: 32128395

Correspondence to A.B. Smit: guus.smit [at] vu.nl
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands. https://mcn.cncr.nl

Protein cross-linking web resource

XL-based protein interaction resource in which each node represents a protein and the edge the protein-protein interaction identified by cross-linking. Protein nodes with black border indicate the identification of intraprotein cross-links. The edge color indicates the individual experiments in which the cross-link was identified. Samples used in this study include synaptosome and microsome fractions purified from hippocampus and cerebellum of mouse brain. Three additional biologically independent replicates were performed for hippocampal synaptosomes. Edge style can be adjusted to display the cross-link identification FDR or the overlap with public protein-protein interaction databases (STRING, BioGRID, InWEB). The filtering options can be used to visualize second order interactions and/or specific subset of experiments. Detailed information on the selected proteins and its cross-links can be found in the different tabs, including in how many samples the interactions were identified, the cross-linking site, brain area and subcellular fraction, confidence in the public PPI databases, etc.

Network view controls

  • Select a protein:
    click a node to center the network on the respective protein or use the search box to find your protein of interest (by official gene symbol). The number in the search box indicates the number of distinct proteins cross-linked to the selected protein. Selecting a node/protein shows its directly cross-linked proteins and, if enabled, also second order interactions. The information about the selected protein is available in the "selected node" tab. Additional details for each cross-link to protein of interest is shown in the "selected node's cross-links" tab.
  • Zoom in/out:
    use the mouse scroll wheel.
  • Move nodes:
    click and drag nodes to change their position.
  • Restore network view:
    click the currently selected protein (in red) to reset the network layout.
A tutorial describing the use and interpretation of the cross-linking network web is available here: download

Data availability

  • The complete dataset can be found as Table S1 in the original publication, [link].
  • The mass spectrometer raw data is available in the PRIDE repository, with identifier PXD010317.
  • The overlap with public PPI databases is based on InWEB (InBio_Map_core_2016_09_12), BioGRID (3.5.165), and StringDB (v10.5), you can see the respective PPI scores in the "selected node's cross-links" tab when expanding the data for any cross-link (click the green plus symbol in the first column).