Insight into the Architecture of the NuRD Complex

作者：Saad AlQarni, Andal Murthy, Wei Zhang, Marcin R. Przewloka, Ana P. G. Silva, Aleksandra A. Watson, Sara Lejon, Xue Pei, Arne H. Smits, Susan L. Kloet, Hongxin Wang, Nicholas E. Shepherd, Philippa H. Stokes, Gerd A. Blobel, Michiel Vermeulen, David M. Glover, Joel P. Mackay, Ernest D. Laue · 发表于：Journal of Biological Chemistry · 年份：2014 · DOI：10.1074/jbc.m114.558940 · 被引用次数：84 · 研究领域：Mitochondrial Function and Pathology、Microtubule and mitosis dynamics、DNA Repair Mechanisms

The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex.