Stabilization of the hexasome intermediate during histone exchange by yeast SWR1 complex

DOI: 10.1016/j.molcel.2024.08.015

Authors: Adam S. B. Jalal (Imperial College London) , Paul Girvan (Imperial College London; MRC Laboratory of Medical Sciences) , Eugene Y. D. Chua (Imperial College London) , Lexin Liu (Imperial College London) , Shijie Wang (Imperial College London) , Elizabeth A. Mccormack (Imperial College London) , Michael T. Skehan (Imperial College London) , Carol L. Knight (Imperial College London) , David S. Rueda (MRC Laboratory of Medical Sciences; Imperial College London) , Dale B. Wigley (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 12

State: Published (Approved)
Published: September 2024
Diamond Proposal Number(s): 36390

Abstract: The yeast SWR1 complex catalyzes the exchange of histone H2A/H2B dimers in nucleosomes with Htz1/H2B dimers. We use cryoelectron microscopy to determine the structure of an enzyme-bound hexasome intermediate in the reaction pathway of histone exchange, in which an H2A/H2B dimer has been extracted from a nucleosome prior to the insertion of a dimer comprising Htz1/H2B. The structure reveals a key role for the Swc5 subunit in stabilizing the unwrapping of DNA from the histone core of the hexasome. By engineering a crosslink between an Htz1/H2B dimer and its chaperone protein Chz1, we show that this blocks histone exchange by SWR1 but allows the incoming chaperone-dimer complex to insert into the hexasome. We use this reagent to trap an SWR1/hexasome complex with an incoming Htz1/H2B dimer that shows how the reaction progresses to the next step. Taken together the structures reveal insights into the mechanism of histone exchange by SWR1 complex.

Diamond Keywords: Fungi

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 05/09/2024 09:56

Documents:
1-s2.0-S1097276524006695-main.pdf

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)