Structural insights into the assembly and dynamics of the ATP-dependent chromatin-remodeling complex SWR1
Contributors: Leschziner, Andres E.; Mango, Susan; Zhuang, Xiaowei; Hogle, Jim
Published: 2014
Language: eng
Description: The ATP-dependent chromatin remodeling complex SWR1 exchanges a variant histone H2A.Z-H2B dimer for a canonical H2A-H2B dimer at nucleosomes flanking histone-depleted regions, such as promoters. This localization of H2A.Z is conserved throughout eukaryotes. SWR1 is a 1 Mega-Dalton complex containing 14 different polypeptides, including the AAA+ ATPases Rvb1 and Rvb2. Using electron microscopy, we obtained the three-dimensional structure of SWR1 and mapped its major functional components. Our data show that SWR1 contains a single hetero-hexameric Rvb1/2 ring that, together with the catalytic subunit Swr1, brackets two independently assembled multi-subunit modules. We also show that SWR1 undergoes a large conformational change upon engaging a limited region of the nucleosome core particle. Our work suggests an important structural role for the Rvb1/2 ring and a distinct substrate-handling mode by SWR1, thereby providing the first structural framework for understanding the complex dimer-exchange reaction.
Notes: Keywords: H2A.Z, Histone exchange, INO80, Nucleosome, Rvb1/Rvb2, Transcription regulation.

Thesis Ph.D. Harvard University 2014