BioGPS Featured Article – Chemoproteomics reveals Toll-like receptor fatty acylation

BioGPS has become the valuable resource that it is because of the contributions from our wonderful user community. Thank you for contributing plugins, suggestions, and ideas–all of which have improved BioGPS for everyone. In order to celebrate the contributions of BioGPS users to the scientific research community, this series will feature publications and articles generated by BioGPS users. We sincerely hope you will join us in celebrating the fascinating work that YOU do.

This week, we will feature an article by collaborating researchers from three institutions across the US: Chemoproteomics reveals Toll-like receptor fatty acylation by Nicholas M Chesarino, Jocelyn C Hach, James L Chen, Balyn W Zaro, Murugesan VS Rajaram, Joanne Turner, Larry S Schlesinger, Matthew R Pratt, Howard C Hang, and Jacob S Yount.

Dr. Jacob Yount kindly answered our inquiries for this series.

1. Who is the team behind the work that was published in Chemoproteomics reveals Toll-like receptor fatty acylation?.
   This work involved a team of immunologists and chemical biologists from the Ohio State University, the Rockefeller University, and the University of Southern California.

 

2. What inspired the work published in Chemoproteomics reveals Toll-like receptor fatty acylation?
   Protein fatty acylation is emerging as a very important type of post-translational modification controlling many aspects of cellular interactions and signaling. Having recently developed chemical tools for identifying and studying new fatty acylated proteins, we were interested in profiling the acylated proteins in different cell types. Our laboratory has a primary interest in antimicrobial immunity so we performed a chemical proteomics screen to identify and compare palmitoylated proteins in mouse embryonic fibroblasts and antigen presenting cells of the immune system known as dendritic cells.

 

3. Please provide a brief summary of the findings reported in your article, Chemoproteomics reveals Toll-like receptor fatty acylation.
   We identified several hundred fatty acylated proteins in fibroblasts and dendritic cells, many of which had never been previously reported to be modified in this way. One of the most exciting and important proteins we identified specifically in dendritic cells was Toll-like receptor 2 (TLR2). TLR2 recognizes a wide array of microbial products and transmits signals for the activation of dendritic cells to induce an immune response. We found that TLR2 fatty acylation, occurring on a single cysteine, promoted its localization at the cell surface and was required for proper induction of inflammatory molecules in response to microbial molecules.

 

4. How did your team utilize BioGPS in this research?
   We utilized bioGPS to determine whether or not there were expression pattern differences in the DHHC palmitoyltransferase enzymes that are known to install a specific type of fatty acylation known as palmitoylation onto proteins. We found that mouse embryonic fibroblasts and mouse dendritic cells express a similar subset of these enzymes, allowing us to discuss that the differences in fatty acylated proteins that we observed between the two cell types was not likely due to differences in the expression of these enzymes, but rather due to cell type-specific expression differences of the specific fatty acylated proteins.

 

5. What are some future directions for the team behind this research?
   We plan to follow up on other TLRs that are palmitoylated in order to determine if fatty acylation has different effects on different TLRs. We also hope to determine whether TLR fatty acylation can be disrupted as a therapeutic approach to inflammatory diseases in which TLRs are over-activated.

 

Thanks again to Dr. Jacob Yount for taking the time to answer our questions. Click here to read their fascinating article. Have a look because these awesome researchers have made their compelling research open access–so you can read the whole exciting article for free!

Used BioGPS and cited it in your publication? Let us know! We would love to feature YOUR work, no matter how long ago it was published. BioGPS Featured Article Series only started recently, but we know your contributions to science is ongoing.