The Role of Posttranslational Acetylation in the Association of Autophagy Protein ATG8 with Microtubules in Plant Cells

Rayevsky, Alexey; Ozheredov, D. S.; Samofalova, Dariia; Ozheredov, S. P.; Karpov, P. A.; Blume, Ya. B.

doi:10.3103/s0095452721060128

Cited by 3 publications

(10 citation statements)

References 53 publications

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“…We used the FT‐Map server to have an idea of the location of the functional areas on the binding site surface. The library of reference compounds included all elements from the ChEMBL database that have functional activity against the FTsZ polymerization process in Mtb and Sa 47 . To eliminate unsuitable substances PAINS filters (Pan Assay INterference Compounds) were used 48 .…”

Section: Methodsmentioning

confidence: 99%

“…The library of reference compounds included all elements from the ChEMBL database that have functional activity against the FTsZ polymerization process in Mtb and Sa. 47 To eliminate unsuitable substances PAINS filters (Pan Assay INterference Compounds) were used. 48 To obtain a set of improved protein-ligand complexes, we applied 4D docking in ICM, the most effective way to account for receptor flexibility using an ensemble of protein conformations from a previously grouped trajectory (Multiple Receptor Conformation).…”

Section: Virtual Screening Approachmentioning

confidence: 99%

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Structure‐based virtual screening and biological evaluation of novel inhibitors of mycobacterium Z‐ring formation

Rayevsky

Dariya

Liudmyla

et al. 2022

J of Cellular Biochemistry

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The major part of commercial prodrugs against Mycobacterium tuberculosis (Mtb) demonstrated a significant inhibitory effect on cell division and inhibition of bacterial growth in vitro. However, further implementation often failed to overcome the compensatory system of interchangeable cascades. This is the most common situation for the compounds, which hit the key enzymes activities involved in all basic stages of the cell cycle. We decided to find more compounds, which could affect a cytoskeleton complex playing important role in sensing the external signals, intracellular transport, and cell division. In general, the bacterial cytoskeleton is crucial for response to the environment and participates in cell-to-cell communication. In turn, filamentous temperature-sensitive Z (FtsZ) protein, a mycobacterial tubulin homolog, is essential for Z-ring formation and further bacteria cell division. We predicted the most preferable binding-sites and conducted a highthroughput virtual screening. Modeling results suggest that some compounds bind in a specific region on the surface Mtb FtsZ, which is absent in human, and other could hit GTPase activity of the FtsZ. Further in vitro studies confirmed that these novel molecules can efficiently bind to these pockets, demonstrating an effect on the polymerization state and kinetics mechanisms.The rescaling of the experiment on the cell line revealed that reported

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Section: Methodsmentioning

confidence: 99%

Section: Virtual Screening Approachmentioning

confidence: 99%

Structure‐based virtual screening and biological evaluation of novel inhibitors of mycobacterium Z‐ring formation

Rayevsky

Dariya

Liudmyla

et al. 2022

J of Cellular Biochemistry

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“…Docking was performed on the based on Ambiguous Interaction Restraints (AIR) obtained from constrained complexes (true interface). For this, all available solvent residues, that could interact with ATG8 (Lys112, Tyr108, Gly410, Glu411, Ser193, Glu155, Met413, Glu415, and Glu417) were selected with at least one heavy atom within 3.9 Å of any heavy atom of the partner molecule (Rayevsky, Ozheredov, et al, 2021). The sampling parameters were stored at default in HADDOCK: 1000 models were generated for rigid body energy minimization (it0), 200 for the semiflexible segment refinement (it1), followed by 200 water refinement steps (itw).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, we started three molecular dynamics simulations of the α-tubulin monomer acetylated at each position. Full details on the conditions and methods for comparative analysis of the trajectories are disclosed in a recent paper on the effects of N-acetylated K40 (Rayevsky, Ozheredov, et al, 2021).…”

Section: Modeling Of All-atom Acetylated States Of Plant α-Tubulinmentioning

confidence: 99%

“…We carefully tested the binding of LC3 (the homologue of ATG8 in human cells) on the tubulin surface using key residues from the literature (Monastyrska et al, 2009). We previously reported the results of our study on the analysis of reconstructed (plant/animal) MT fragments and surface probing (Rayevsky et al, 2019, Rayevsky, Ozheredov, et al, 2021.…”

Section: Structural Prerequisites Leading To the Formation Of The Mic...mentioning

confidence: 99%

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In silico induced effect of N‐ε‐lysine acetylation on microtubule stability and subsequent interaction of microtubule‐associated proteins

Rayevsky

Elijah

Sharifi

et al. 2023

Cell Biology International

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Plant systems have been considered valuable models for addressing fundamental questions of microtubule (MT) organization due to their considerable practical utility. Protein acetylation is a very common protein modification, and therate of acetylation can be modulated in cells in different biological states, and these changes can be detected at a molecular level. Here, we focused on K40, K112, and K394 residues as putative acetylation sites, which were shown to exist in both plants and mammals. Such residual effect of acetylation causes critical but unclear effect on MT stability. In turn, it was shown that acetylation indirectly affects the probability of interaction with different MAPs (Microtubule‐associated proteins). In a multiscale study using an all‐atom force field to reproduce several lattice‐forming elements found on the surface the microtubule, we assembled a fragment of a plant microtubule composed of nine tubulins and used it as a model object along with the existing human complex. Triplets of tubulins assembled in a lattice cell were then simulated for both human and plant protein complexes, using a coarse‐grained force field. We then analyzed the trajectories and identified some critical deformations of the MAP interaction surface. The initial coordinates were used to investigate the structural scenario in which autophagy‐related protein 8 (ATG8) was able to interact with the MT fragment.

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Structural flexibility and shape similarity contribute to exclusive functions of certain ATG8 isoforms in the autophagy process

Bulgakov,

Rayevsky,

Blume

et al. 2024

Preprint

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One of them relates to the curious interactions between certain ATG8 isoforms and its receptors/adaptors in plants during the autophagy process. These proteins ultimately regulate the initiation, expansion and maturation of the phagophore, which acts as a docking platform for numerous autophagy proteins. The bioinformatician analysis of the human, yeast and plant amino acid sequences allowed us to split them into groups and determine the head-liners taking the experimental data into account. We conducted a structure-based study aimed to identify some hidden reasons for the differences in selectivity of ATG8 isoforms. A series of molecular dynamics simulations were run in attempt to explain the ATG8s’ stage-dependent functionality. The canonic secondary structure organization and folding of all ATG8 proteins and therefore almost identical PPI interface areas make this investigation particularly important and interesting. Aware of the dual role of the ATG8 interacting motif (W/F/Y-X-X-X-L/I/V) in autophagosome biogenesis and the recruitment of an anchored selective autophagy receptor (SAR), we conducted a mobility domain analysis. To this end, sequence of amino acids associated with the LDS interface was localized and underwent an RMSD-based clustering analysis. The resulting ATG8-peptide complexes reflected significant binding preferences of different ATG8 isotypes.

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The Role of Posttranslational Acetylation in the Association of Autophagy Protein ATG8 with Microtubules in Plant Cells

Cited by 3 publications

References 53 publications

Structure‐based virtual screening and biological evaluation of novel inhibitors of mycobacterium Z‐ring formation

Structure‐based virtual screening and biological evaluation of novel inhibitors of mycobacterium Z‐ring formation

In silico induced effect of N‐ε‐lysine acetylation on microtubule stability and subsequent interaction of microtubule‐associated proteins

Structural flexibility and shape similarity contribute to exclusive functions of certain ATG8 isoforms in the autophagy process

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