Dynamics and Mechanisms in the Recruitment and Transference of Histone Chaperone CIA/ASF1

Zhang, Yanjun; Tao, Huanyu; Huang, Sheng‐You

doi:10.3390/ijms20133325

Cited by 5 publications

(3 citation statements)

References 69 publications

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“…All the MD simulations included two stages: Minimization and equilibration [45,46,47]. The minimization included three steps: The systems were first subjected to 2500 steps of steep descent movements, followed by 2500 steps of conjugate gradient minimization to remove the bad clashes between solute and solvent.…”

Section: Methodsmentioning

confidence: 99%

Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA

Zhang

Huang

2019

IJMS

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The well-known mismatch repair (MMR) machinery, MutS/MutL, is absent in numerous Archaea and some Bacteria. Recent studies have shown that EndoMS/NucS has the ability to cleave double-stranded DNA (dsDNA) containing a mismatched base pair, which suggests a novel mismatch repair process. However, the recognition mechanism and the binding process of EndoMS/NucS in the MMR pathway remain unclear. In this study, we investigate the binding dynamics of EndoMS/NucS to mismatched dsDNA and its energy as a function of the angle between the two C-terminal domains of EndoMS/NucS, through molecular docking and extensive molecular dynamics (MD) simulations. It is found that there exists a half-open transition state corresponding to an energy barrier (at an activation angle of approximately 80 ∘ ) between the open state and the closed state, according to the energy curve. When the angle is larger than the activation angle, the C-terminal domains can move freely and tend to change to the open state (local energy minimum). Otherwise, the C-terminal domains will interact with the mismatched dsDNA directly and converge to the closed state at the global energy minimum. As such, this two-state system enables the exposed N-terminal domains of EndoMS/NucS to recognize mismatched dsDNA during the open state and then stabilize the binding of the C-terminal domains of EndoMS/NucS to the mismatched dsDNA during the closed state. We also investigate how the EndoMS/NucS recognizes and binds to mismatched dsDNA, as well as the effects of K + ions. The results provide insights into the recognition and binding mechanisms of EndoMS/NucS to mismatched dsDNA in the MMR pathway.

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Section: Methodsmentioning

confidence: 99%

Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA

Zhang

Huang

2019

IJMS

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“…In addition, IE63 was found to be able to lock part of anti–silencing factor 1 (ASF1) into the cytoplasm in a model of latent VZV infection of enteric neurons in guinea pigs ( Ambagala et al, 2009 ). ASF1, a member of the H3/H4 family of histone chaperones, is a nucleosome assembly factor that participates in a variety of cellular functions, including DNA replication, gene transcription, and the cellular response to DNA damage by histone removal from and deposition onto DNA ( Donham et al, 2011 ; Zhang et al, 2018 , 2019 ; Cote et al, 2019 ). In VZV-infected and IE-63–transfected cells, ASF1 colocalized and immunoprecipitated with IE-63.…”

Section: Roles Of Icp22/orf63 In Viral Latency and Reactivationmentioning

confidence: 99%

Multifaceted Roles of ICP22/ORF63 Proteins in the Life Cycle of Human Herpesviruses

Yang

Wang

et al. 2021

Front. Microbiol.

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Herpesviruses are extremely successful parasites that have evolved over millions of years to develop a variety of mechanisms to coexist with their hosts and to maintain host-to-host transmission and lifelong infection by regulating their life cycles. The life cycle of herpesviruses consists of two phases: lytic infection and latent infection. During lytic infection, active replication and the production of numerous progeny virions occur. Subsequent suppression of the host immune response leads to a lifetime latent infection of the host. During latent infection, the viral genome remains in an inactive state in the host cell to avoid host immune surveillance, but the virus can be reactivated and reenter the lytic cycle. The balance between these two phases of the herpesvirus life cycle is controlled by broad interactions among numerous viral and cellular factors. ICP22/ORF63 proteins are among these factors and are involved in transcription, nuclear budding, latency establishment, and reactivation. In this review, we summarized the various roles and complex mechanisms by which ICP22/ORF63 proteins regulate the life cycle of human herpesviruses and the complex relationships among host and viral factors. Elucidating the role and mechanism of ICP22/ORF63 in virus–host interactions will deepen our understanding of the viral life cycle. In addition, it will also help us to understand the pathogenesis of herpesvirus infections and provide new strategies for combating these infections.

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“…The large variability of peptide ligands necessitates the systematic investigation of various MD parameters like simulation length, temperature, water model, restraints, clustering, etc. In this study, we focused on histone H3 peptides in complexes with their reader proteins that have crucial therapeutic, as well as diagnostic, importance in various cancers and other diseases [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. At the same time, histones are particularly challenging ligands for molecular docking as they often interact with shallow binding pockets on the reader proteins with weak interactions measured in micromolar binding constants [ 94 ].…”

Section: Introductionmentioning

confidence: 99%

Efficient Refinement of Complex Structures of Flexible Histone Peptides Using Post-Docking Molecular Dynamics Protocols

Bayarsaikhan,

Zsidó,

Börzsei

et al. 2024

IJMS

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Histones are keys to many epigenetic events and their complexes have therapeutic and diagnostic importance. The determination of the structures of histone complexes is fundamental in the design of new drugs. Computational molecular docking is widely used for the prediction of target–ligand complexes. Large, linear peptides like the tail regions of histones are challenging ligands for docking due to their large conformational flexibility, extensive hydration, and weak interactions with the shallow binding pockets of their reader proteins. Thus, fast docking methods often fail to produce complex structures of such peptide ligands at a level appropriate for drug design. To address this challenge, and improve the structural quality of the docked complexes, post-docking refinement has been applied using various molecular dynamics (MD) approaches. However, a final consensus has not been reached on the desired MD refinement protocol. In this present study, MD refinement strategies were systematically explored on a set of problematic complexes of histone peptide ligands with relatively large errors in their docked geometries. Six protocols were compared that differ in their MD simulation parameters. In all cases, pre-MD hydration of the complex interface regions was applied to avoid the unwanted presence of empty cavities. The best-performing protocol achieved a median of 32% improvement over the docked structures in terms of the change in root mean squared deviations from the experimental references. The influence of structural factors and explicit hydration on the performance of post-docking MD refinements are also discussed to help with their implementation in future methods and applications.

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Dynamics and Mechanisms in the Recruitment and Transference of Histone Chaperone CIA/ASF1

Cited by 5 publications

References 69 publications

Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA

Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA

Multifaceted Roles of ICP22/ORF63 Proteins in the Life Cycle of Human Herpesviruses

Efficient Refinement of Complex Structures of Flexible Histone Peptides Using Post-Docking Molecular Dynamics Protocols

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