Dynamic BTB-domain filaments promote clustering of ZBTB proteins.

The formation of dynamic protein filaments contributes to various biological functions by clustering individual molecules together and enhancing their binding to ligands. We report such a propensity for the BTB domains of certain proteins from the ZBTB family, a large eukaryotic transcription factor family implicated in differentiation and cancer. Working with Xenopus laevis and human proteins, we solved the crystal structures of filaments formed by dimers of the BTB domains of ZBTB8A and ZBTB18 and demonstrated concentration-dependent higher-order assemblies of these dimers in solution. In cells, the BTB-domain filamentation supports clustering of full-length human ZBTB8A and ZBTB18 into dynamic nuclear foci and contributes to the ZBTB18-mediated repression of a reporter gene. The BTB domains of up to 21 human ZBTB family members and two related proteins, NACC1 and NACC2, are predicted to behave in a similar manner. Our results suggest that filamentation is a more common feature of transcription factors than is currently appreciated. [Display omitted] • BTB domains of some vertebrate proteins form dynamic filaments composed of dimers • We characterized BTB-domain filaments from ZBTB8A and ZBTB18 • Filaments cluster these proteins into foci and contribute to their function • This behavior might extend to numerous ZBTB family and related proteins Mance et al. found that the BTB domains of certain vertebrate ZBTB proteins, including ZBTB8A and ZBTB18, can form dynamic filaments composed of dimers. Molecular clustering mediated by this process dictates the localization of full-length ZBTB proteins into nuclear foci and contributes to their function as gene repressors. [ABSTRACT FROM AUTHOR]