Total chemical synthesis of glycosylated TREM2 ectodomain
Wijegunawardena, Gayani Castillo, Erika Henrickson, Brandy Davis, Regan Condello, Carlo Wu, Haifan
Wijegunawardena, Gayani
Castillo, Erika
Henrickson, Brandy
Davis, Regan
Condello, Carlo
Wu, Haifan
Citations
Altmetric:
Other Names
Location
Time Period
Advisors
Original Date
Digitization Date
Issue Date
2023-06-07
Type
Article
Genre
Keywords
TREM2,Native chemical ligation,Glycosylation,Alzheimer's disease
Subjects (LCSH)
Citation
Gayani Wijegunawardena, Erika Castillo, Brandy Henrickson, Regan Davis, Carlo Condello, and Haifan Wu
ACS Chemical Neuroscience 2023 14 (11), 2243-2251
DOI: 10.1021/acschemneuro.3c00257
Abstract
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.
Table of Contents
Description
Click on the DOI to access the publisher's version of this article.
Publisher
American Chemical Society
Journal
Book Title
Series
ACS Chemical Neuroscience
Volume 14, No. 11
Volume 14, No. 11
Digital Collection
Finding Aid URL
Use and Reproduction
Archival Collection
PubMed ID
DOI
ISSN
1948-7193