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Title 

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

Authors 

Seung Jun KimDae Gwin JeongSook Kyung JeongTae-Sung YoonSeong Eon Ryu

Publisher 

American Diabetes Association

Issue Date 

2007

Citation 

Diabetes, vol. 56, no. 1, pp. 41-48

Keywords 

autoantigeninsulinoma associated protein 2protein tyrosine phosphatasecrystal structurediabetes mellitusprotein domainprotein structurestructure analysisautoantigenscrystallography, 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 

http://dx.doi.org/10.2337/db06-0237

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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