SNAP output for PDB entry 6m6a [SNAP web server]

PDB-id

6m6a; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription

Method

cryo-EM (5.0 Å)

Summary

cryo-EM structure of thermus thermophilus mfd in complex with RNA polymerase

Reference

Shi J, Wen A, Zhao M, Jin S, You L, Shi Y, Dong S, Hua X, Zhang Y, Feng Y (2020): "Structural basis of Mfd-dependent transcription termination." Nucleic Acids Res., 48, 11762-11772. doi: 10.1093/nar/gkaa904.

Abstract

Mfd-dependent transcription termination plays an important role in transcription-coupled DNA repair, transcription-replication conflict resolution, and antimicrobial resistance development. Despite extensive studies, the molecular mechanism of Mfd-dependent transcription termination in bacteria remains unclear, with several long-standing puzzles. How Mfd is activated by stalled RNA polymerase (RNAP) and how activated Mfd translocates along the DNA are unknown. Here, we report the single-particle cryo-electron microscopy structures of T. thermophilus Mfd-RNAP complex with and without ATPγS. The structures reveal that Mfd undergoes profound conformational changes upon activation, contacts the RNAP β1 domain and its clamp, and pries open the RNAP clamp. These structures provide a foundation for future studies aimed at dissecting the precise mechanism of Mfd-dependent transcription termination and pave the way for rational drug design targeting Mfd for the purpose of tackling the antimicrobial resistance crisis.