Recognition of dimethylarginine analogues by tandem Tudor domain protein Spindlin1
Epigenetic readout of the combinatorial posttranslational modification comprised of trimethyllysine and asymmetric dimethylarginine (H3K4me3R8me2a) takes place via biomolecular recognition of tandem Tudor-domain-containing protein Spindlin1. Through comparative thermodynamic data and molecular dynam...
| المؤلفون الرئيسيون: | , , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
MDPI
2022
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| _version_ | 1826307730201116672 |
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| author | Porzberg, MRB Moesgaard, L Johansson, C Oppermann, U Kongsted, J Mecinović, J |
| author_facet | Porzberg, MRB Moesgaard, L Johansson, C Oppermann, U Kongsted, J Mecinović, J |
| author_sort | Porzberg, MRB |
| collection | OXFORD |
| description | Epigenetic readout of the combinatorial posttranslational modification comprised of trimethyllysine and asymmetric dimethylarginine (H3K4me3R8me2a) takes place via biomolecular recognition of tandem Tudor-domain-containing protein Spindlin1. Through comparative thermodynamic data and molecular dynamics simulations, we sought to explore the binding scope of asymmetric dimethylarginine mimics by Spindlin1. Herein, we provide evidence that the biomolecular recognition of H3K4me2R8me2a is not significantly affected when R8me2a is replaced by dimethylarginine analogues, implying that the binding of K4me3 provides the major binding contribution. High-energy water molecules inside both aromatic cages of the ligand binding sites contribute to the reader–histone association upon displacement by histone peptide, with the K4me3 hydration site being lower in free energy due to a flip of Trp151. |
| first_indexed | 2024-03-07T07:07:31Z |
| format | Journal article |
| id | oxford-uuid:408c8974-ccca-458b-8a93-24dd9be9b0ba |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:07:31Z |
| publishDate | 2022 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oxford-uuid:408c8974-ccca-458b-8a93-24dd9be9b0ba2022-05-19T14:34:09ZRecognition of dimethylarginine analogues by tandem Tudor domain protein Spindlin1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:408c8974-ccca-458b-8a93-24dd9be9b0baEnglishSymplectic ElementsMDPI2022Porzberg, MRBMoesgaard, LJohansson, COppermann, UKongsted, JMecinović, JEpigenetic readout of the combinatorial posttranslational modification comprised of trimethyllysine and asymmetric dimethylarginine (H3K4me3R8me2a) takes place via biomolecular recognition of tandem Tudor-domain-containing protein Spindlin1. Through comparative thermodynamic data and molecular dynamics simulations, we sought to explore the binding scope of asymmetric dimethylarginine mimics by Spindlin1. Herein, we provide evidence that the biomolecular recognition of H3K4me2R8me2a is not significantly affected when R8me2a is replaced by dimethylarginine analogues, implying that the binding of K4me3 provides the major binding contribution. High-energy water molecules inside both aromatic cages of the ligand binding sites contribute to the reader–histone association upon displacement by histone peptide, with the K4me3 hydration site being lower in free energy due to a flip of Trp151. |
| spellingShingle | Porzberg, MRB Moesgaard, L Johansson, C Oppermann, U Kongsted, J Mecinović, J Recognition of dimethylarginine analogues by tandem Tudor domain protein Spindlin1 |
| title | Recognition of dimethylarginine analogues by tandem Tudor domain protein Spindlin1 |
| title_full | Recognition of dimethylarginine analogues by tandem Tudor domain protein Spindlin1 |
| title_fullStr | Recognition of dimethylarginine analogues by tandem Tudor domain protein Spindlin1 |
| title_full_unstemmed | Recognition of dimethylarginine analogues by tandem Tudor domain protein Spindlin1 |
| title_short | Recognition of dimethylarginine analogues by tandem Tudor domain protein Spindlin1 |
| title_sort | recognition of dimethylarginine analogues by tandem tudor domain protein spindlin1 |
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