Mechanism of DNA translocation underlying chromatin remodelling by Snf2

Li, M.; Xia, Xian; Tian, Yuan; Jia, Qiong; Liu, X.; Lu, Yinying; Li, Xiangdong; Chen, Z.

doi:10.1038/s41586-019-1029-2

Cited by 120 publications

(184 citation statements)

References 40 publications

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“…Fig 4a-d). Overall, our RSC SAR -nucleosome structure shows a RecA ATPase bound to the nucleosome at superhelical location 2 (SHL2), consistent with previous cryo-EM structures 19,29,30 . Surprisingly, the ARP module extends from the N-terminus of the ATPase domain, lying roughly on the same plane as the nucleosome (Fig.…”

Section: Cryo-em Structure Of a Regulated Rsc Subcomplexsupporting

confidence: 89%

Structural insights into assembly and function of the RSC chromatin remodeling complex

Leschziner

Baker

Reimer

et al. 2020

Preprint

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Chromatin remodelers regulate the position and composition of nucleosomes throughout the genome, producing different remodeling outcomes despite a shared underlying mechanism based on a conserved RecA DNA translocase. How this functional diversity is achieved remains unknown despite recent cryo-electron microscopy (cryo-EM) reconstructions of several remodelers, including the yeast RSC complex. To address this, we have focused on a RSC subcomplex comprising its ATPase (Sth1), the essential actin-related proteins (ARPs) Arp7 and Arp9, and the fungal-specific protein Rtt102. Combining cryo-EM and biochemistry of this subcomplex, which exhibits regulation of remodeling by the ARPs, we show that ARP binding induces a helical conformation in the HSA domain of Sth1, which bridges the ATPase domain with the bulk of the complex. Surprisingly, the ARP module is rotated by 120º in the subcomplex relative to full RSC about a pivot point previously identified as a regulatory hub in Sth1, suggesting that large conformational changes are part of Sth1 regulation and RSC assembly. We also show that an interaction between Sth1 and the nucleosome acidic patch, which appears to be conserved among SWI/SNF remodelers, enhances remodeling. Taken together, our structural data shed light on the assembly and function of the RSC complex.

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Section: Cryo-em Structure Of a Regulated Rsc Subcomplexsupporting

confidence: 89%

Structural insights into assembly and function of the RSC chromatin remodeling complex

Leschziner

Baker

Reimer

et al. 2020

Preprint

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“…We do not observe any density for the ATPase domain of Sth1; however, based on the structure of the Sth1 homolog Snf2 bound to the NCP, we expect the catalytic subunit to bind super-helical location-2 (SHL2) ( Fig. 3c) 21 . In the resulting model, the N and C termini of adjacent Sth1 domains are at the right distance to connect through the short linkers between them ( Fig.…”

mentioning

confidence: 82%

“…We were able to accurately fit our structure of the RSC core within this map, along with models of the Arp module (Arp7, Arp9, Rtt102 and Sth1-HSA) and the NCP ( Fig. 3c) 18,21 . About 88% (206/233) of mappable crosslinks in our model of the RSC-Arp module structure are within 38 Å distance (Fig 3b, Fig.…”

mentioning

confidence: 84%

“…The model of the RSC-NCP complex was generated by docking our model of the RSC core, the crystal structure of the Arp module (PDB 4I6M: Arp7, Arp9, Rtt102 and Snf2-HSA) and cryo-EM structure of Snf2-MMTV nucleosome complex bound at the SHL2 with ADP (PDB 6IY2: Snf2, nucleosome) 18,21 . The sequence for the Snf2-HSA helix in 4I6M and Snf2 helicase domain in 6IY2 were aligned to the Sth1 sequence and mutated in COOT 46 .…”

Section: Model Building and Refinementmentioning

confidence: 99%

“…The ATPase (not visible in our density) is modeled according to the structure of nucleosome-bound Snf2 (ref. 21 ). c, Interactions between the RSC core and the nucleosome.…”

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confidence: 99%

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Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement

Patel

Moore

Greber

et al. 2019

Preprint

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Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility 1,2 . The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a member of the SWI/SNF chromatin remodeler family, plays critical roles in genome maintenance, transcription, and DNA repair 2-4 . Here we report cryo-electron microscopy (cryo-EM) and crosslinking mass spectrometry (CLMS) studies of yeast RSC complex and show that RSC is composed of a rigid tripartite core and two flexible lobes. The core structure is scaffolded by an asymmetric Rsc8 dimer and built with the evolutionarily conserved subunits Sfh1, Rsc6, Rsc9 and Sth1. The flexible ATPase lobe, composed of helicase subunit Sth1, Arp7, Arp9 and Rtt102, is anchored through the interactions between the N-terminus of Sth1 and the core. Our cryo-EM analysis also shows that in addition to the expected nucleosome-Sth1 interactions, RSC engages histones and nucleosomal DNA through one arm of the core structure, composed of Rsc8 SWRIM domains, Sfh1 and Npl6. Our findings provide structural insights into the conserved assembly process for all members of the SWI/SNF family of remodelers, and illustrate how RSC selects, engages, and remodels nucleosomes. MainEukaryotes have four major families of chromatin remodelers: SWI/SNF, ISWI, CHD, and INO80 2 . Each of these remodelers plays distinct roles based on how they select and affect target nucleosomes. Together, these remodelers give rise to the distinct chromatin landscapes observed in eukaryotic cells and determine how genetic information is organized, replicated, transcribed, and repaired 5 . In S. cerevisiae there are two members of the SWI/SNF family of chromatin remodelers: RSC and SWI/SNF 3,4 . RSC is essential for viability and is ten times more abundant than SWI/SNF 4 . While both complexes play a role in remodeling nucleosomes during transcription initiation, RSC is also involved in transcription-independent processes such as mitotic division, double stranded break repair, and telomere maintenance 6-12 .RSC is a ~1-MDa complex composed of 17 proteins, with two copies of Rsc8 and one copy of either Rsc1 or Rsc2 (Fig. S1) 4,13 . In order to determine the structure of RSC, we purified the complex from S. cerevisiae and performed cryo-EM analysis (Fig. S2). We find that RSC is composed of five main lobes, three that form a rigid core (head, body and arm) and two that are flexibly attached (leg and tail) ( Fig. 1a, b; Fig. S3, S4). We determined the structure of the core to ~3.1 Å and mapped 14 proteins within this region: Rsc1/2, Rsc3, Rsc4, Rsc6, Rsc8 (2 copies), Rsc9, Rsc30, Rsc58, Ldb7, Npl6, Htl1, Sfh1, and Sth1 (Fig. 1c, d, e). Our negative stain analysis of the yeast SWI/SNF complex shows that, like RSC, it has head, body, and arm regions that define a rigid core, and a flexible leg that occupies similar overall positions (Fig. S5). However, SWI/SNF lacks a tail lobe, indicating that while RSC and SWI/SNF share a conserved core architecture, ...

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Four Parallel Pathways in T4 Ligase‐Catalyzed Repair of Nicked DNA with Diverse Bending Angles

Li,

Ma,

et al. 2024

Advanced Science

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The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase–AMP complex and the ligase–AMP–DNA complex can have four conformations. This finding suggests the parallel occurrence of four ligation reaction pathways, each characterized by specific conformations of the ligase–AMP complex that persist in the ligase–AMP–DNA complex. Notably, these complexes have DNA bending angles of ≈0°, 20°, 60°, or 100°. The mechanism of parallel reactions challenges the conventional notion of simple sequential reaction steps occurring among multiple conformations. The results provide insights into the dynamic conformational changes and the versatile attributes of T4 DNA ligase and suggest that the parallel multiple reaction pathways may correspond to diverse T4 DNA ligase functions. This mechanism may potentially have evolved as an adaptive strategy across evolutionary history to navigate complex environments.

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Mechanism of DNA translocation underlying chromatin remodelling by Snf2

Cited by 120 publications

References 40 publications

Structural insights into assembly and function of the RSC chromatin remodeling complex

Structural insights into assembly and function of the RSC chromatin remodeling complex

Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement

Four Parallel Pathways in T4 Ligase‐Catalyzed Repair of Nicked DNA with Diverse Bending Angles

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