Crystal structure of the major diabetes autoantigen insulinoma-associated protein 2 reveals distinctive immune epitopes

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Title
Crystal structure of the major diabetes autoantigen insulinoma-associated protein 2 reveals distinctive immune epitopes
Author(s)
Seung Jun KimDae Gwin Jeong; Sook Kyung Jeong; Tae-Sung Yoon; Seong Eon Ryu
Bibliographic Citation
Diabetes, vol. 56, no. 1, pp. 41-48
Publication Year
2007
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
Publisher
Amer Diabetes Assoc
DOI
http://dx.doi.org/10.2337/db06-0237
Type
Article
Appears in Collections:
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
Division of Research on National Challenges > Bionanotechnology Research Center > 1. Journal Articles
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