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Mol Cell ; 84(13): 2490-2510.e9, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38996459

RESUMO

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.


Assuntos
Domínio BTB-POZ , Fatores de Transcrição , Proteínas de Xenopus , Animais , Humanos , Núcleo Celular/metabolismo , Núcleo Celular/genética , Cristalografia por Raios X , Células HEK293 , Modelos Moleculares , Ligação Proteica , Multimerização Proteica , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/química , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Xenopus laevis , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/química
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