Protein crotonylation is the chemical reaction between crotonic acid and protein. The reaction results in formation of crotonyl-CoA derivatives from amino acids. This article will provide a detailed overview of the biological function of protein crotonylation. Existing chemicals for protein crotonylation inhibition will also be discussed.
Crotonylation Gets Some Attention
Crotonylation has been getting some attention lately. This modification is a covalent attachment of crotonate to proteins, and researchers are finding it modulates many different functions in cells. It’s not a modification that people were thinking of when they started looking for post-translational modifications (PTMs) on proteins, but now it appears to be as prevalent as acetylation or phosphorylation.
In the past couple years, scientists have discovered that crotonylation is important in a number of cellular processes, including:
* epigenetic regulation of gene expression
* cell cycle control
* protein folding
* transcriptional regulation
* suppression of inflammation
Protein Crotonylation in the Cell
Protein crotonylation is a newly discovered post-translational protein modification that may be found in all organisms. Crotonylated lysine residues are generated through the action of histone crotonyltransferases (HCTs) that use crotonyl-CoA as the donor substrate.
HCTs are recruited to the nucleus by WRAD, a protein that binds to WRAD motifs in HCTs. The discovery of crotonylation, its substrates and regulators has opened up new avenues for investigation into the role of this modification in cells and organisms. Protein crotonylation has been correlated with cell proliferation and stress response, but other potential roles remain unexplored.
Crotonylation could be a key modification in several important cellular processes, including signaling through nuclear receptors and crosstalk with other modifications. In this article, I review our current knowledge of protein crotonylation and its potential roles in transcriptional regulation and crosstalk with other modifications.
Chemical Probes for Crotonylation
A Chemical Probe for Protein Crotonylation Explains the Role of Crotonylation in Cancer and Fertility.
Protein activities are regulated by multiple posttranslational modifications (PTMs), including acetylation, phosphorylation, and glycosylation. Although many of these modifications have been used to regulate protein functions, we still know little about the roles of other types of PTMs, such as crotonylation. The mechanisms underlying the function of crotonylation are poorly understood.
The crotonyl-CoA carboxylase/reductase (CCR) is responsible for catalysing the conversion of crotonyl-CoA to butyryl-CoA. This process regulates the level of endogenous protein crotonylation through a “crotonate shunt” mechanism by relieving CCR inhibition with butyryl-CoA product. Interestingly, this mechanism has been shown to be crucial for tumorigenesis in colorectal cancer; however, further research is required to elucidate the precise mechanism underlying this process.
The Newest Chemical Probe for Protein Crotonylation
The regulation of proteins through chemical modifications is an important control point in many biological processes. One example is the covalent addition of an acyl group to a protein, also known as protein crotonylation. This modification is found in all three domains of life and has been linked to a variety of biological functions and diseases in mammals. However, due to its low abundance, protein crotonylation remains difficult to study using existing techniques.
Now, a team led by researchers from Tokyo-based RIKEN has developed a chemical probe for studying protein crotonylation in living cells. In their Cell Chemical Biology paper, the researchers describe the probe and use it to reveal new information about where on proteins this modification occurs and how it affects protein function.
“We are very excited by our findings,” says Hiroaki Suga, leader of the RIKEN Advanced Center for Computing and Communication (ACCC) Proteomics Unit, who led the study with ACCC’s Koji Yamamoto. “Our probe will be useful not only for visualizing protein crotonylation but also for identifying its substrates.”
Probing into The Biology of Protein Crotonlylation
Protein crotonylation is a recently identified PTM (Post-Translational Modification) that plays an important role in metabolic homeostasis and cellular stress response. Although the biological function of protein crotonylation has been extensively investigated, it is still difficult to study the crotonylation site because of the lack of a specific detection method.
In this paper, a chemoenzymatic strategy for selective protein crotonylation labeling using a genetically encoded acyl-CoA synthetase was developed. The gene of acyl-CoA synthetase was introduced into E. coli cells to catalyze propionyl-CoA into crotonyl-CoA, which acted as an intermediate substrate for crotonylating protein lysine residues.
With the help of NMR spectroscopy and mass spectrometry (MS), proteins containing crotonlylation can be detected directly in cell lysates and tissue extracts. This technique provides a valuable tool to understand the biology of protein crotonlylation.
Last Words
A new chemical probe allows scientists to detect the presence of crotonylated proteins in cell and tissue samples, a modification that could be involved in diabetes, cancer and aging. The newly published probe could be used to detect protein crotonylation in cell and tissue samples. It works by fluorescently tagging crotonylated proteins in a sample, allowing scientists to see where they are.