Topic
Methyllysine
About: Methyllysine is a research topic. Over the lifetime, 134 publications have been published within this topic receiving 6598 citations.
Papers published on a yearly basis
Papers
TL;DR: Structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9 suggest a role for cation-π and van der Waals interactions, with trimethylation slightly improving the binding affinity.
Abstract: The chromodomain of the HP1 family of proteins recognizes histone tails with specifically methylated lysines. Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing. The histone tail inserts as a β strand, completing the β-sandwich architecture of the chromodomain. The methylammonium group is caged by three aromatic side chains, whereas adjacent residues form discerning contacts with one face of the chromodomain. Comparison of dimethyl- and trimethyllysine-containing complexes suggests a role for cation-π and van der Waals interactions, with trimethylation slightly improving the binding affinity.
886 citations
TL;DR: Structural, biophysical, and mutagenic approaches are employed to characterize the molecular determinants of sequence contextual methyllysine binding to human Cbx1–8 proteins and explain the divergence of peptide binding selectivity in the Pc subfamily.
317 citations
TL;DR: G9a and GLP contain a new type of methyllysine binding module (the ankyrin repeat domains) and are the first examples of protein (histone) methyltransferases harboring in a single polypeptide the activities that generate and read the same epigenetic mark.
Abstract: Histone modifications have important roles in transcriptional control, mitosis and heterochromatin formation. G9a and G9a-like protein (GLP) are euchromatin-associated methyltransferases that repress transcription by mono- and dimethylating histone H3 at Lys9 (H3K9). Here we demonstrate that the ankyrin repeat domains of G9a and GLP bind with strong preference to N-terminal H3 peptides containing mono- or dimethyl K9. X-ray crystallography revealed the basis for recognition of the methylated lysine by a partial hydrophobic cage with three tryptophans and one acidic residue. Substitution of key residues in the cage eliminated the H3 tail interaction. Hence, G9a and GLP contain a new type of methyllysine binding module (the ankyrin repeat domains) and are the first examples of protein (histone) methyltransferases harboring in a single polypeptide the activities that generate and read the same epigenetic mark.
285 citations
TL;DR: This review will focus on chemical and biochemical aspects in addition, recognition, and removal of this posttranslational mark of protein lysine methylation.
Abstract: Protein lysine methylation is a distinct posttranslational modification that causes minimal changes in the size and electrostatic status of lysine residues. Lysine methylation plays essential roles in regulating fates and functions of target proteins in an epigenetic manner. As a result, substrates and degrees (free versus mono/di/tri) of protein lysine methylation are orchestrated within cells by balanced activities of protein lysine methyltransferases (PKMTs) and demethylases (KDMs). Their dysregulation is often associated with neurological disorders, developmental abnormalities, or cancer. Methyllysine-containing proteins can be recognized by downstream effector proteins, which contain methyllysine reader domains, to relay their biological functions. While numerous efforts have been made to annotate biological roles of protein lysine methylation, limited work has been done to uncover mechanisms associated with this modification at a molecular or atomic level. Given distinct biophysical and biochemical ...
211 citations
TL;DR: An unexpected mode of peptide-mediated dimerization suggests a possible mechanism for chromatin compaction by L3MBTL1.
Abstract: Crystal structures of the L3MBTL1 MBT repeats in complex with histone H4 peptides dimethylated on Lys20 (H4K20me2) show that only the second of the three MBT repeats can bind mono- and dimethylated histone peptides. Its binding pocket has similarities to that of 53BP1 and is able to recognize the degree of histone lysine methylation. An unexpected mode of peptide-mediated dimerization suggests a possible mechanism for chromatin compaction by L3MBTL1.
208 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 7 |
| 2020 | 13 |
| 2019 | 9 |
| 2018 | 10 |
| 2017 | 7 |
| 2016 | 12 |