Novel intermolecular zinc fingers and redox-driven conformational changes dictate tumor suppressor ZMYND11's role in cooperative recognition of diverse targets.

ABSTRACT: The zinc finger-myeloid-Nervy-DEAF-1 (ZMYND) protein family is associated with embryonic development and cancer regulation. Specifically, the tumor suppressor ZMYND11 is downregulated in multiple malignancies. Here, we identified an inhibitory role of ZMYND11 in colorectal cancers and determined crystal structures of the winged helix domain (WH), a plant homeodomain (PHD), coiled-coil-MYND (CC-MYND) domains, and their complex with an adenovirus E1A peptide. Unexpectedly, intermolecular zinc finger and intermolecular disulfide bonds were found for domains PHD and WH/CC-MYND, respectively. Interestingly, the oligomeric state of the PHD domain was pH-dependent, and the redox state of the CC domain impaired the binding, such as in the tumor or inflammatory microenvironments. Moreover, these co

SUBMITTER: Bai X 

PROVIDER: S-EPMC12839526 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature