Macromolecular complexes are involved in a broad spectrum of cellular processes including protein biosynthesis, protein secretion and degradation, metabolism, DNA replication and repair, and signal transduction along with other important biological processes. The analysis of protein complexes in health and disease is important to gain insights into cellular physiology and pathophysiology. In the last few decades, research has focused on the identification and the dynamics of macromolecular complexes. Several techniques have been developed to isolate native protein complexes from cells and tissues to allow further characterization by microscopic and proteomic analysis. In the present paper, we provide a brief overview of proteomic methods that can be used to identify protein–protein interactions, focusing on recent developments to study the entire complexome of a biological sample.

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