SETD3 protein is the actin-specific histidine N-methyltransferase

@article{Kwiatkowski2018SETD3PI,
  title={SETD3 protein is the actin-specific histidine N-methyltransferase},
  author={Sebastian Kwiatkowski and Agnieszka Kinga Seliga and Didier Vertommen and Marianna Terreri and Takao Ishikawa and Iwona Grabowska and Marcel Tiebe and Aurelio A. Teleman and Adam K. Jagielski and Maria Veiga-da-Cunha and Jakub Drożak},
  journal={eLife},
  year={2018},
  volume={7}
}
Protein histidine methylation is rarely studied posttranslational modification of unknown biochemical importance. In vertebrates, only a few methylhistidne-containing proteins have been reported so far, including β-actin as an essential example. The evolutionary conserved methylation of β-actin H73 residue is catalyzed by a specific histidine N-methyltransferase that has never been identified molecularly. In the present investigation, we have purified actin-specific histidine N… 
The Structure, Activity, and Function of the SETD3 Protein Histidine Methyltransferase
TLDR
The discovery of numerous novel methyltransferase interactors suggests that SETD3 may regulate various biological processes, including cell cycle and apoptosis, carcinogenesis, response to hypoxic conditions, and enterovirus pathogenesis.
Protein histidine methylation.
TLDR
This review aims to summarize the recent advances in the understanding of the chemical, enzymological and physiological aspects of protein histidine methylation.
Molecular basis for histidine N3-specific methylation of actin H73 by SETD3
TLDR
The structural basis for histidine N1-specific methylation by SETD3 is revealed and conserved overall substrate engagement mode, in which both peptide substrates are bound at the inner β-edge of sheet III with actin H73 and histone H3K36M, highlighting a role of histidine methylation in regulating cell motility.
Characterization of SETD3 methyltransferase–mediated protein methionine methylation
TLDR
The results suggest that placing methionine properly in the active site—within close proximity to and in line with the incoming methyl group of SAM—would allow some SET domain proteins to selectively methylate methionines in proteins.
SETD3 is an Actin Histidine Methyltransferase that Prevents Primary Dystocia
TLDR
SETD3 methylates mammalian actin at His73, and SETD3 deficiency impairs stimulus-induced contraction in primary human uterine smooth muscle cells and leads to maternal dystocia in mice, which supports the broader hypothesis that protein histidine methylation acts as a common regulatory mechanism.
Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function
TLDR
METTL18 is established as the second human histidine-specific protein MTase, and its functional relevance is demonstrated, indicating that METTL18-mediated methylation of RPL3 is important for optimal ribosome biogenesis and function.
Structural insights into SETD3-mediated histidine methylation on beta-actin.
TLDR
This study is the first to show a catalytic mechanism of SETD3-mediated histidinemethylation on β-actin, which not only throws light on the protein histidine methylation phenomenon but also facilitates the design of small molecule inhibitors ofSETD3.
The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes
TLDR
It is reported that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes, and the results establishMETTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.
Structural basis for the target specificity of actin histidine methyltransferase SETD3
TLDR
SETD3 is the first known metazoan protein histidine methyltransferase but the molecular basis for its target specificity is unclear and the authors elucidate the structural and molecular determinants for the histidine specificity of SETD3.
METTL18-mediated histidine methylation of RPL3 modulates translation elongation for proteostasis maintenance
TLDR
It is reported that human METTL18 is a histidine methyltransferase for the ribosomal protein RPL3 and that the modification specifically slows ribosome traverse on tyrosine codons, allowing the proper folding of synthesized proteins.
...
...

References

SHOWING 1-10 OF 90 REFERENCES
The use of alternative substrates in the characterization of actin-methylating and carnosine-methylating enzymes.
TLDR
Two potential alternative substrates have been investigated and a chicken beta-actin expressed in Escherichia coli as a fusion protein with 80 amino acids of an influenza protein, NS1, and a synthetic peptide corresponding to residues 69-77 of actin are investigated.
A highly conserved 3-methylhistidine modification is absent in yeast actin.
TLDR
It is found that His-73 is not modified, and the methodology for the analytical determination of 3-methylhistidine in actin offers an improved approach for investigating histidine methylation in proteins.
SETD3 is an Actin Histidine Methyltransferase that Prevents Primary Dystocia
TLDR
SETD3 methylates mammalian actin at His73, and SETD3 deficiency impairs stimulus-induced contraction in primary human uterine smooth muscle cells and leads to maternal dystocia in mice, which supports the broader hypothesis that protein histidine methylation acts as a common regulatory mechanism.
A Novel 3-Methylhistidine Modification of Yeast Ribosomal Protein Rpl3 Is Dependent upon the YIL110W Methyltransferase*
TLDR
It is shown that Rpl3, a protein of the large ribosomal subunit from baker's yeast, is stoichiometrically monomethylated at position 243, producing a 3-methylhistidine residue, the first report of a methylated histidine residue in yeast cells, and the first example of a gene required for protein histidine methylation in nature.
Protein lysine methylation by seven-β-strand methyltransferases.
TLDR
A number of novel 7BS KMTs have now been discovered, and, in particular, several recently characterized human and yeast members of MTase family 16 (MTF16) have been found to methylate lysines in non-histone proteins.
Histidine Methylation of Yeast Ribosomal Protein Rpl3p Is Required for Proper 60S Subunit Assembly
TLDR
It is proposed that Hpm1p plays a role in the orchestration of the early assembly of the large ribosomal subunit and in faithful protein production.
UPF0586 Protein C9orf41 Homolog Is Anserine-producing Methyltransferase*
TLDR
It is concluded that UPF0586 is mammalian carnosine N-methyltransferase and hypothesize that it may also serve as a peptide or protein methyltransferase in eukaryotes.
Protein arginine methyltransferase 1: positively charged residues in substrate peptides distal to the site of methylation are important for substrate binding and catalysis.
TLDR
Inhibition studies suggest that potent and selective bisubstrate analogue inhibitor(s) for PRMT1 can be developed by linking a histone based peptide substrate to homocysteine or sinefungin, and evidence is presented thatPRMT1 utilizes a partially processive mechanism to dimethylate its substrates.
The role of MeH73 in actin polymerization and ATP hydrolysis.
TLDR
It was found that H73A-actin exchanged ATP at an increased rate, and was less stable than yeast-expressed wild-type actin, indicating that the mutation affects the spatial relationship between the two domains of actin which embrace the nucleotide.
...
...