TY - JOUR
T1 - XMolecular architecture of the ATP-dependent chromatin-remodeling complex SWR1
AU - Nguyen, Vu Q.
AU - Ranjan, Anand
AU - Stengel, Florian
AU - Wei, Debbie
AU - Aebersold, Ruedi
AU - Wu, Carl
AU - Leschziner, Andres E.
N1 - Funding Information:
We would like to thank Sjors Scheres (LMB-MRC, Cambridge), Pawel Penczek (University of Texas, Houston), John Rubinstein (University of Toronto), and Niko Grigorieff (Janelia Farm) for technical advice, Katerina Toropova, Rogelio Hernandez-Lopez, and Michael Cianfrocco in the Leschziner Lab for contributions during this work, Samara Reck-Peterson (Harvard Medical School), Andrew Richardson, Yoel Stuart, Beka Buckman, and Steve Klosterman (Harvard University) for feedback on the manuscript, Rachelle Gaudet and Nicole Francis (Harvard University) for advice, and Locksley for moral support. EM data were collected at Harvard’s Center for Nanoscale Systems, a member of the National Nanotechnology Infrastructure Network and supported by the National Science Foundation (NSF) (ECS-0335765). Computation was performed in part on the Odyssey cluster supported by Harvard’s FAS Science Division Research Computing Group. V.Q.N. was supported by the Joint Training Program in Molecules, Cells and Organisms funded by the National Institutes of Health (NIH) (GM007598) and a NSF Graduate Research Fellowship. A.R. was supported in part by a fellowship from the Leukemia and Lymphoma Society. F.S. is a Sir Henry Wellcome Fellow (Wellcome Trust Grant 095951). A.E.L. was supported in part by a fellowship from the Alfred P. Sloan Foundation. This project was supported by grants from the NIH (R01 GM092895A) (to A.E.L.), ETH Zurich (to R.A.), the Commission of the European Communities through the PROSPETS consortium (EU FP7 projects 201648 and 233226 to R.A.), the European Research Council (ERC-2008-AdG 233226 to R.A.), the Center for Cancer Research, National Cancer Institute (to A.R., D.W., and C.W.), and the Howard Hughes Medical Institute (C.W.).
PY - 2013/9/12
Y1 - 2013/9/12
N2 - 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 megadalton 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 heterohexameric Rvb1/Rvb2 ring that, together with the catalytic subunit Swr1, brackets two independently assembled multisubunit 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 Rvbs and a distinct substrate-handling mode by SWR1, thereby providing a structural framework for understanding the complex dimer-exchange reaction.
AB - 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 megadalton 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 heterohexameric Rvb1/Rvb2 ring that, together with the catalytic subunit Swr1, brackets two independently assembled multisubunit 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 Rvbs and a distinct substrate-handling mode by SWR1, thereby providing a structural framework for understanding the complex dimer-exchange reaction.
UR - https://www.scopus.com/pages/publications/84884225242
UR - https://www.scopus.com/pages/publications/84884225242#tab=citedBy
U2 - 10.1016/j.cell.2013.08.018
DO - 10.1016/j.cell.2013.08.018
M3 - Article
C2 - 24034246
AN - SCOPUS:84884225242
SN - 0092-8674
VL - 154
SP - X1220-1231
JO - Cell
JF - Cell
IS - 6
ER -