Exploration of the structural and functional diversity in the metamorphic RfaH subfamily

About 14% of predicted RfaH homologs are predominantly in an active, NusG-like fold state, and in vivo they show constitutive activity comparable to known RfaH mutants.

• Why it matters: RfaH’s fold-switching is thought to enable selective control of distant virulence genes, but how monomorphic, always-active variants evolved from NusG-like ancestors is unclear.
• What they did: Using AlphaFold2, thousands of RfaH homologs were modeled to find a subset (~14%) predicted to remain active, then in vivo assays tested constitutive transcription/translation activity.
• The result: Monomorphic homologs cluster into a distinct phylogenetic clade and are preferentially found within or next to long virulence-associated operons, supporting stepwise specialization via structural transformation.

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