Structure of the frequency‐interacting RNA helicase: a protein interaction hub for the circadian clock

FRH may mediate interactions among key proteins in the Neurospora crassa circadian clock.

• The protein complex of frequency (FRQ), casein kinase 1a (CK1a), and FRH represses gene expression rhythmically.
• Crystal structures of FRH show differences from its yeast homolog Mtr4, highlighting its unique role in the circadian clock.
• A mutation (R806H) that disrupts circadian rhythms is located on a positively charged surface of the KOW domain, which is distant from the helicase core.
• Mutations in other nearby residues can affect binding interactions with the white-collar complex (WCC) and FRQ.
• An alteration (V142G) near the N-terminus of FRQ changes its binding to both FRH and WCC, resulting in a shorter clock period.
• FRH's helicase activity is not essential for the circadian clock; instead, it facilitates protein interactions through its N-terminus and KOW module.

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