Insights into association of the NuRD complex with FOG-1 from the crystal structure of an RbAp48·FOG-1 complex.
Insights into association of the NuRD complex with FOG-1 from the crystal structure of an RbAp48·FOG-1 complex.
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DOI：
10.1074/jbc.m110.195842
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发表时间：
2011-01-14
期刊：
影响因子：
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通讯作者：
Mackay JP
中科院分区：
文献类型：
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作者：
Lejon S;Thong SY;Murthy A;AlQarni S;Murzina NV;Blobel GA;Laue ED;Mackay JP
染色质修饰复合物（例如 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，人们对这些相互作用的分子基础知之甚少。在这里，我们展示了与 GATA-1 辅因子 FOG-1 的 15 个 N 端氨基酸结合的 NuRD 亚基 RbAp48 的 1.9 Å 分辨率晶体结构。 FOG-1 肽与 RbAp48 β-螺旋桨顶部的带负电荷的结合袋接触，该结合袋不同于 RpAp48 用于接触组蛋白 H4 的结合表面。我们进一步表明，RbAp48 通过与其 FOG 结合口袋不同的表面与 NuRD 亚基 MTA-1 相互作用，从而首次了解 NuRD 组装促进与辅因子相互作用的方式。我们的 RbAp48·FOG-1 结构提供了对 FOG-1 依赖性与 NuRD 复合物关联的分子决定因素以及转录调控和核小体重塑之间联系的深入了解。
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.