PeerJ | |
An in silico study of how histone tail conformation affects the binding affinity of ING family proteins | |
article | |
Nadir Gül1  Ahmet Yıldız2  | |
[1] Faculty of Natural Sciences, Turkish-German University;Faculty of Engineering, Turkish-German University | |
关键词: Epigenetics; Histone Tail; ING Protein; In silico; Binding affinity; Molecular docking; Intrinsically Disordered Proteins; | |
DOI : 10.7717/peerj.14029 | |
学科分类:社会科学、人文和艺术(综合) | |
来源: Inra | |
【 摘 要 】
BackgroundDue to its intrinsically disordered nature, the histone tail is conformationally heterogenic. Therefore, it provides specific binding sites for different binding proteins or factors through reversible post-translational modifications (PTMs). For instance, experimental studies stated that the ING family binds with the histone tail that has methylation on the lysine in position 4. However, numerous complexes featuring a methylated fourth lysine residue of the histone tail can be found in the UniProt database. So the question arose if other factors like the conformation of the histone tail affect the binding affinity.MethodsThe crystal structure of the PHD finger domain from the proteins ING1, ING2, ING4, and ING5 are docked to four histone H3 tails with two different conformations using Haddock 2.4 and ClusPro. The best four models for each combination are selected and a two-sample t-test is performed to compare the binding affinities of helical conformations vs. linear conformations using Prodigy. The protein-protein interactions are examined using LigPlot.ResultsThe linear histone conformations in predicted INGs-histone H3 complexes exhibit statistically significant higher binding affinity than their helical counterparts (confidence level of 99%). The outputs of predicted models generated by the molecular docking programs Haddock 2.4 and ClusPro are comparable, and the obtained protein-protein interaction patterns are consistent with experimentally confirmed binding patterns.ConclusionThe results show that the conformation of the histone tail is significantly affecting the binding affinity of the docking protein. Herewith, this in silico study demonstrated in detail the binding preference of the ING protein family to histone H3 tail. Further research on the effect of certain PTMs on the final tail conformation and the interaction between those factors seem to be promising for a better understanding of epigenetics.
【 授权许可】
CC BY
【 预 览 】
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