Discovery and significance of protein-protein interactions in health and disease
- Cell. 2024 Nov 14;187(23):6501-6517. doi: 10.1016/j.cell.2024.10.038.
- 1. Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada. Electronic address: [email protected].
- 2. Department of Biochemistry and Biophysics, University of California, San Francisco (UCSF), San Francisco, CA, USA.
- 3. Quantitative Biosciences Institute, University of California, San Francisco (UCSF), San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco (UCSF), San Francisco, CA, USA. Electronic address: [email protected].
The identification of individual protein-protein interactions (PPIs) began more than 40 years ago, using protein affinity chromatography and antibody co-immunoprecipitation. As new technologies emerged, analysis of PPIs increased to a genome-wide scale with the introduction of intracellular tagging methods, affinity purification (AP) followed by mass spectrometry (MS), and co-fractionation MS (CF-MS). Now, combining the resulting catalogs of interactions with complementary methods, including crosslinking MS (XL-MS) and cryogenic electron microscopy (cryo-EM), helps distinguish direct interactions from indirect ones within the same or between different protein complexes. These powerful approaches and the promise of artificial intelligence applications like AlphaFold herald a future where PPIs and protein complexes, including energy-driven protein machines, will be understood in exquisite detail, unlocking new insights in the contexts of both basic biology and disease.