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

Science Advances
M A Gonzalez-LozanoA B Smit

Abstract

Synaptic transmission is the predominant form of communication in the brain. It requires functionally specialized molecular machineries constituted by thousands of interacting synaptic proteins. Here, we made use of recent advances in cross-linking mass spectrometry (XL-MS) in combination with biochemical and computational approaches to reveal the architecture and assembly of synaptic protein complexes from mouse brain hippocampus and cerebellum. We obtained 11,999 unique lysine-lysine cross-links, comprising connections within and between 2362 proteins. This extensive collection was the basis to identify novel protein partners, to model protein conformational dynamics, and to delineate within and between protein interactions of main synaptic constituents, such as Camk2, the AMPA-type glutamate receptor, and associated proteins. Using XL-MS, we generated a protein interaction resource that we made easily accessible via a web-based platform (http://xlink.cncr.nl) to provide new entries into exploration of all protein interactions identified.

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Citations

Nov 20, 2020·Amino Acids·Péter GulyássyKatalin Adrienna Kékesi
Oct 8, 2020·International Journal of Molecular Sciences·Sofiia ReshetniakChristian Tetzlaff
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Aug 19, 2021·Chemical Reviews·Rivkah Rogawski, Michal Sharon
Sep 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Johannes F HevlerAlbert J R Heck

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Datasets Mentioned

BETA
PXD010317
PXD015160

Methods Mentioned

BETA
x-ray crystallography
cross-linking assay
peptide array
Protein Array

Software Mentioned

MS2
Scwrl4
Proteome Discoverer
MS
Loop
HADDOCK2
Protein Array Analyzer for ImageJ
SynGO
DisVis Webserver
SYBYL

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