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Title | Crystal structure of the major diabetes autoantigen insulinoma-associated protein 2 reveals distinctive immune epitopes |
Authors | Seung Jun Kim; Dae Gwin Jeong; Sook Kyung Jeong; Tae-Sung Yoon; Seong Eon Ryu |
Publisher | American Diabetes Association |
Issue Date | 2007 |
Citation | Diabetes, vol. 56, no. 1, pp. 41-48 |
Keywords | autoantigen; insulinoma associated protein 2; protein tyrosine phosphatase; crystal structure; diabetes mellitus; protein domain; protein structure; structure analysis; autoantigens; crystallography, X-ray |
Abstract | Insulinoma-associated protein-2 (IA-2) is a major autoantigen in type 1 diabetes that occurs through autoimmunemediated β-cell destruction. We present here the crystal structure of the protein tyrosine phosphatase (PTP)-like domain of human IA-2. The structure reveals a canonical PTP domain with the closed WPD loop over the active site pocket, explaining the lack of enzyme activity in the native protein. The structural interpretation of previous mutagenesis studies indicates that the B-cell epitopes are concentrated on two distinctive regions on peripheral loops of the central β-sheet surrounding T-cell epitopes within the sheet. The detailed structural information on immune epitopes provides a framework for the future development of immune intervention strategies against diabetes. |
ISSN | 0012-1797 |
Link | |
Appears in Collections | |
Registered Date |
2019-05-02 |
