9W3E

Cryo-EM structure of E. coli RNA polymerase in complex with PP1

Summary for 9W3E

• Entry DOI: 10.2210/pdb9w3e/pdb
• EMDB information: 65598
• Descriptor: DNA-directed RNA polymerase subunit alpha, DNA-directed RNA polymerase subunit beta, DNA-directed RNA polymerase subunit beta', ... (5 entities in total)
• Functional Keywords: alphafold 3, transcription regulation, phage, rna polymerase, sigma factor, transcription
• Biological source: Escherichia coli; More
• Total number of polymer chains: 6
• Total formula weight: 403529.27

Authors

Yuan, L.,Feng, Y. (deposition date: 2025-07-29, release date: 2026-04-29)

Primary citation

Yuan, L.,Liu, Q.,Xiao, X.,Xu, L.,Liang, L.,Guo, Y.,Yao, Y.,Wang, H.,Feng, Y.,Hua, X.,Feng, Y.
AlphaFold 3-powered discovery of phage proteins that inhibit bacterial transcription initiation.
Cell Rep, 45:117082-117082, 2026

PubMed Abstract: Many 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.

PubMed: 41824451
DOI: 10.1016/j.celrep.2026.117082

Experimental method

ELECTRON MICROSCOPY (3.6 Å)