Structural highlights
Publication Abstract from PubMedMany phages encode proteins that specifically inhibit host RNA polymerase activity, thereby sabotaging and, in some cases, hijacking the host transcription machinery to serve their needs. Traditional methods for identifying new phage proteins that inhibit bacterial transcription are labor intensive and require access to live phages. To overcome these limitations, we develop a highly efficient pipeline for AlphaFold 3-guided discovery of phage proteins that inhibit bacterial transcription initiation. Using this pipeline, three phage proteins are identified and characterized. Structural and biochemical analyses demonstrate that these phage proteins bind to distinct sites on RNA polymerase and inhibit transcription initiation via different mechanisms. This study showcases the power of AlphaFold 3 in discovering novel binders of large protein complexes, and the pipeline developed here could be readily adapted to screen modulators of other large targets, such as the ribosome, proteasome, and CRISPR-Cas systems. AlphaFold 3-powered discovery of phage proteins that inhibit bacterial transcription initiation.,Yuan L, Liu Q, Xiao X, Xu L, Liang L, Guo Y, Yao Y, Wang H, Feng Y, Hua X, Feng Y Cell Rep. 2026 Mar 24;45(3):117082. doi: 10.1016/j.celrep.2026.117082. Epub 2026 , Mar 12. PMID:41824451[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 08:29, 29 April 2026.