动态 BTB 结构域丝促进 ZBTB 蛋白的聚集。
Dynamic BTB-domain filaments promote clustering of ZBTB proteins.
发表日期：2024 Jul 11
作者：
Lucija Mance, Nicolas Bigot, Edison Zhamungui Sánchez, Franck Coste, Natalia Martín-González, Siham Zentout, Marin Biliškov, Zofia Pukało, Aanchal Mishra, Catherine Chapuis, Ana-Andreea Arteni, Axelle Lateur, Stéphane Goffinont, Virginie Gaudon, Ibtissam Talhaoui, Ignacio Casuso, Martine Beaufour, Norbert Garnier, Franck Artzner, Martine Cadene, Sébastien Huet, Bertrand Castaing, Marcin Józef Suskiewicz
来源：
MOLECULAR CELL
摘要：
动态蛋白丝的形成通过将单个分子聚集在一起并增强它们与配体的结合来促进各种生物功能。我们报告了 ZBTB 家族某些蛋白质的 BTB 结构域的这种倾向，ZBTB 家族是一个与分化和癌症有关的大型真核转录因子家族。通过利用非洲爪蟾和人类蛋白质，我们解析了由 ZBTB8A 和 ZBTB18 的 BTB 结构域二聚体形成的丝的晶体结构，并证明了这些二聚体在溶液中的浓度依赖性高阶组装。在细胞中，BTB 结构域丝化支持全长人类 ZBTB8A 和 ZBTB18 聚集成动态核灶，并有助于 ZBTB18 介导的报告基因抑制。预计多达 21 个人类 ZBTB 家族成员和两种相关蛋白 NACC1 和 NACC2 的 BTB 结构域具有相似的行为方式。我们的结果表明，丝状化是转录因子的一个比目前人们认识到的更常见的特征。版权所有 © 2024 Elsevier Inc. 保留所有权利。
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.Copyright © 2024 Elsevier Inc. All rights reserved.