Regulation of Rvb1/Rvb2 by a Domain within the INO80 Chromatin Remodeling Complex Implicates the Yeast Rvbs as Protein Assembly Chaperones

Zhou, Coral Y.; Stoddard, Caitlin I.; Johnston, Jonathan B.; Trnka, Michael J.; Echeverria, Ignacia; Palovcak, Eugene; Šali, Andrej; Burlingame, Alma L.; Cheng, Yifan; Narlikar, Geeta J.

doi:10.1016/j.celrep.2017.05.029

Cited by 48 publications

(52 citation statements)

References 46 publications

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“…RuvBL1 and RuvBL2 are homologous proteins with 43% sequence identity and 65% sequence similarity that work together as part of chromatin remodeling complexes 4 , 8 , 29 – 31 . However, they also work antagonistically in many situations.…”

Section: Resultsmentioning

confidence: 99%

“…It is in fact possible that the functions of the external region of domain II may be in great part related to its interaction (mediated by the N-terminal loop) with the nucleotide in the binding pocket, with a concomitant motion with as yet undefined consequences. One of these could be the observed disassembly of dodecameric RuvBL1/2 into hexamers upon incubation with ATP 29 . It is also worth noting that the OB-fold comprises distinct superfamilies, and while the most common relates to nucleic acid-binding, they can also occur in larger proteins as recognition domains, and have even been found at protein-protein interfaces 27 .…”

Section: Discussionmentioning

confidence: 99%

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X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action

Silva¹,

Brito²,

Arranz³

et al. 2018

Sci Rep

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RuvB-Like transcription factors function in cell cycle regulation, development and human disease, such as cancer and heart hyperplasia. The mechanisms that regulate adenosine triphosphate (ATP)-dependent activity, oligomerization and post-translational modifications in this family of enzymes are yet unknown. We present the first crystallographic structure of full-length human RuvBL2 which provides novel insights into its mechanistic action and biology. The ring-shaped hexameric RuvBL2 structure presented here resolves for the first time the mobile domain II of the human protein, which is responsible for protein-protein interactions and ATPase activity regulation. Structural analysis suggests how ATP binding may lead to domain II motion through interactions with conserved N-terminal loop histidine residues. Furthermore, a comparison between hsRuvBL1 and 2 shows differences in surface charge distribution that may account for previously described differences in regulation. Analytical ultracentrifugation and cryo electron microscopy analyses performed on hsRuvBL2 highlight an oligomer plasticity that possibly reflects different physiological conformations of the protein in the cell, as well as that single-stranded DNA (ssDNA) can promote the oligomerization of monomeric hsRuvBL2. Based on these findings, we propose a mechanism for ATP binding and domain II conformational change coupling.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action

Silva¹,

Brito²,

Arranz³

et al. 2018

Sci Rep

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show abstract

“…Loss of these proteins confers sensitivity to metabolic stress, polyploidy, and reduces cellular fitness ( Chambers et al 2012 ; Yao et al 2016 ; Gowans et al 2018 ). Interestingly, INO80-C subunits may pre-assemble before integrating into the complex ( Yao et al 2016 ; Zhou et al 2017 ).…”

mentioning

confidence: 99%

Identification of Two Distinct Classes of the Human INO80 Complex Genome-Wide

Runge

Raab²,

Magnuson

2018

G3 Genes|Genomes|Genetics

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Chromatin remodeling and histone modifying enzymes play a critical role in shaping the regulatory output of a cell. Although much is known about these classes of proteins, identifying the mechanisms by which they coordinate gene expression programs remains an exciting topic of investigation. One factor that may contribute to the targeting and activity of chromatin regulators is local chromatin landscape. We leveraged genomic approaches and publically-available datasets to characterize the chromatin landscape at targets of the human INO80 chromatin remodeling complex (INO80-C). Our data revealed two classes of INO80-C targets with distinct chromatin signatures. The predominant INO80-C class was enriched for open chromatin, H3K27ac, and representative subunits from each of the three INO80-C modules (RUVBL1, RUVBL2, MCRS1, YY1). We named this class Canonical INO80. Notably, we identified an unexpected class of INO80-C targets that contained only the INO80 ATPase and harbored a repressive chromatin signature characterized by inaccessible chromatin, H3K27me3, and the methyltransferase EZH2. We named this class Non-Canonical INO80 (NC-INO80). Biochemical approaches indicated that INO80-C and the H3K27 acetyltransferase P300 physically interact, suggesting INO80-C and P300 may jointly coordinate chromatin accessibility at Canonical INO80 sites. No interaction was detected between INO80-C and EZH2, indicating INO80-C and EZH2 may engage in a separate form of regulatory crosstalk at NC-INO80 targets. Our data indicate that INO80-C is more compositionally heterogenous at its genomic targets than anticipated. Moreover, our data suggest there is an important link between INO80-C and histone modifying enzymes that may have consequences in developmental and pathological contexts.

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“…Finally, our statistical test applies to independent samples from a stochastic algorithm such as Monte Carlo sampling, whereas some other methods do not require the samples to be independent (36)(37)(38)(39)(40). Preliminary versions of our sampling exhaustiveness protocol have been already used in several integrative modeling applications (9)(10)(11)(61)(62)(63). Earlier, sampling exhaustiveness for integrative modeling was estimated, at best, by manual visual inspection of localization densities of clusters (7,8,44).…”

Section: Relation To Prior Workmentioning

confidence: 99%

Assessing Exhaustiveness of Stochastic Sampling for Integrative Modeling of Macromolecular Structures

Viswanath

Chemmama

Cimermančič

et al. 2017

Biophysical Journal

Self Cite

142

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Modeling of macromolecular structures involves structural sampling guided by a scoring function, resulting in an ensemble of good-scoring models. By necessity, the sampling is often stochastic, and must be exhaustive at a precision sufficient for accurate modeling and assessment of model uncertainty. Therefore, the very first step in analyzing the ensemble is an estimation of the highest precision at which the sampling is exhaustive. Here, we present an objective and automated method for this task. As a proxy for sampling exhaustiveness, we evaluate whether two independently and stochastically generated sets of models are sufficiently similar. The protocol includes testing 1) convergence of the model score, 2) whether model scores for the two samples were drawn from the same parent distribution, 3) whether each structural cluster includes models from each sample proportionally to its size, and 4) whether there is sufficient structural similarity between the two model samples in each cluster. The evaluation also provides the sampling precision, defined as the smallest clustering threshold that satisfies the third, most stringent test. We validate the protocol with the aid of enumerated good-scoring models for five illustrative cases of binary protein complexes. Passing the proposed four tests is necessary, but not sufficient for thorough sampling. The protocol is general in nature and can be applied to the stochastic sampling of any set of models, not just structural models. In addition, the tests can be used to stop stochastic sampling as soon as exhaustiveness at desired precision is reached, thereby improving sampling efficiency; they may also help in selecting a model representation that is sufficiently detailed to be informative, yet also sufficiently coarse for sampling to be exhaustive.

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Regulation of Rvb1/Rvb2 by a Domain within the INO80 Chromatin Remodeling Complex Implicates the Yeast Rvbs as Protein Assembly Chaperones

Cited by 48 publications

References 46 publications

X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action

X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action

Identification of Two Distinct Classes of the Human INO80 Complex Genome-Wide

Assessing Exhaustiveness of Stochastic Sampling for Integrative Modeling of Macromolecular Structures

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