The NuRD complex is essential for normal development and regulates both gene transcription and DNA damage repair. We have used structural, biophysical and biochemical data to define the architecture of the native mammalian complex. We showed that the complex displays considerable dynamics and we identified stable subcomplexes within NuRD, showing that the full complex is composed of two parts with separable enzymatic activities. A pseudo-symmetric deacetylase module comprising MTA, HDAC and RBBP subunits; whereas MBD, GATAD2 and CHD subunits form an asymmetric 1:1:1 arrangement with remodelling activity. The previously enigmatic GATAD2 both controls the asymmetry in the complex and recruits the ATP-dependent CHD remodeller. Taken together, our data define the architecture of the intact NuRD complex, revealing its structural dynamics and functional plasticity.