دورية أكاديمية
Total chemical synthesis of glycosylated TREM2 ectodomain
| العنوان: | Total chemical synthesis of glycosylated TREM2 ectodomain |
|---|---|
| المؤلفون: | Wijegunawardena, Gayani, Castillo, Erika, Henrickson, Brandy, Davis, Regan, Condello, Carlo, Wu, Haifan |
| بيانات النشر: | American Chemical Society |
| سنة النشر: | 2023 |
| المجموعة: | Wichita State University: SOAR (Shocker Open Access Repository) |
| مصطلحات موضوعية: | TREM2, Native chemical ligation, Glycosylation, Alzheimer's disease |
| الوصف: | Click on the DOI to access the publisher's version of this article. ; Mutations in a microglia-associated gene TREM2 increase the risk of Alzheimer's disease. Currently, structural and functional studies of TREM2 mainly rely on recombinant TREM2 proteins expressed from mammalian cells. However, using this method, it is difficult to achieve site-specific labeling. Here, we present the total chemical synthesis of the 116 amino acid TREM2 ectodomain. Rigorous structural analysis ensured correct structural fold after refolding. Treating microglial cells with refolded synthetic TREM2 enhanced microglial phagocytosis, proliferation, and survival. We also prepared TREM2 constructs with defined glycosylation patterns and found that glycosylation at N79 is critical to the thermal stability of TREM2. This method will provide access to TREM2 constructs with site-specific labeling, such as fluorescent labeling, reactive chemical handles, and enrichment handles, to further advance our understanding of TREM2 in Alzheimer's disease. ; This research was supported by a startup fund from Wichita State University, Ralph E. Powe Junior Faculty Enhancement Award from ORAU, and these NIH grants R15AG080493 (H.W.), RF1AG061874 (C.C.), and P01AG002132 (C.C.). The authors thank Drs. Chamani Perera and Eden Go in the University of Kansas Synthetic Chemical Biology Core Facility (P20GM113117) for their help with mass analysis using MALDI-TOF, Hayden Thurman for help with mass analysis using an Orbitrap mass spectrometer, and Dr. Sam Mackintosh in IDeA National Resource for Quantitative Proteomics (R24GM137786) for help with XL-MS. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1948-7193 |
| العلاقة: | ACS Chemical Neuroscience; Volume 14, No. 11; https://doi.org/10.1021/acschemneuro.3c00257Test; https://soar.wichita.edu/handle/10057/25480Test |
| DOI: | 10.1021/acschemneuro.3c00257 |
| الإتاحة: | https://doi.org/10.1021/acschemneuro.3c00257Test https://soar.wichita.edu/handle/10057/25480Test |
| حقوق: | © 2023 American Chemical Society |
| رقم الانضمام: | edsbas.BFDA99A9 |
| قاعدة البيانات: | BASE |
| تدمد: | 19487193 |
|---|---|
| DOI: | 10.1021/acschemneuro.3c00257 |