Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
J Biol Chem. 2011 Jan 14;286(2):1196-203. doi: 10.1074/jbc.M110.195842. Epub 2010 Nov 2.
Chromatin-modifying complexes such as the NuRD complex are recruited to particular genomic sites by gene-specific nuclear factors. Overall, however, little is known about the molecular basis for these interactions. Here, we present the 1.9 Å resolution crystal structure of the NuRD subunit RbAp48 bound to the 15 N-terminal amino acids of the GATA-1 cofactor FOG-1. The FOG-1 peptide contacts a negatively charged binding pocket on top of the RbAp48 β-propeller that is distinct from the binding surface used by RpAp48 to contact histone H4. We further show that RbAp48 interacts with the NuRD subunit MTA-1 via a surface that is distinct from its FOG-binding pocket, providing a first glimpse into the way in which NuRD assembly facilitates interactions with cofactors. Our RbAp48·FOG-1 structure provides insight into the molecular determinants of FOG-1-dependent association with the NuRD complex and into the links between transcription regulation and nucleosome remodeling.
染色质修饰复合物，如 NuRD 复合物，通过基因特异性核因子被招募到特定的基因组位点。然而，总的来说，对于这些相互作用的分子基础知之甚少。在这里，我们呈现了分辨率为 1.9 Å 的 NuRD 亚基 RbAp48 与 GATA-1 辅助因子 FOG-1 的 N 端 15 个氨基酸的晶体结构。FOG-1 肽与 RbAp48 β-推进器顶部的带负电荷的结合口袋接触，该口袋与 RpAp48 接触组蛋白 H4 的结合表面不同。我们进一步表明，RbAp48 通过与 FOG 结合口袋不同的表面与 NuRD 亚基 MTA-1 相互作用，这为了解 NuRD 组装如何促进与辅助因子的相互作用提供了第一印象。我们的 RbAp48·FOG-1 结构提供了对 FOG-1 依赖性与 NuRD 复合物结合的分子决定因素的深入了解，以及转录调控和核小体重塑之间的联系。
