Nature https://doi.org/10.1038/s41586-021-03592-2 (2021).
Eukaryotic cells are partitioned into distinct compartments, which orchestrate the multitude of biochemical processes that sustain complex life. Defining the composition of these discrete intracellular environments is essential to understand the inner workings of a cell. Addressing this need, Anne-Claude Gingras and colleagues used a proximity-dependent biotinylation approach (BioID) to chart the human cell. The research team tagged 234 intracellular marker proteins, so-called ‘baits,’ with a variant of a biotin ligase that covalently labels lysine residues within a radius of approximately 10 nm of the bait protein and identified modified proteins (‘prey’) via mass spectrometry. The bait proteins covered 32 different cellular compartments, such as the plasma membrane, sections of the endoplasmic reticulum or mitochondria, endosomes, chromatin and the nucleoplasm, thus allowing the authors to define the organization of the cellular proteome. Baits that reside in the same cellular compartment had similar interaction profiles, but even within these groups, specific proximal interactions between protein subsets could be identified. About half of the assigned protein localizations were previously reported, demonstrating the reliability of the predictions made by the BioID data. The authors further confirm the localization of a subset of poorly studied proteins via immunofluorescence microscopy. They also demonstrate that their data can be mined to reveal new protein functions by analyzing a subset of proteins associated with both mitochondria or peroxisomes and ER-membrane compartments, which were shown to impact mitochondrial homeostasis. To aid exploration of the dataset, the authors created humancellmap.org, a community resource that provides online tools for protein localization analysis. The website allows users to compare their own BioID data to the database, and future developments will include further integration of publicly available datasets. If you ever wonder where your favorite protein resides within the cell, you now know where to look.
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