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Updated: Jul 18, 2026

Extraction of Tissue Antigens for Functional Assays
Published on: September 10, 2012
Crystal structure of the major diabetes autoantigen insulinoma-associated protein 2 reveals distinctive immune
Seung Jun Kim1, Dae Gwin Jeong, Sook Kyung Jeong
1Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Euh-eun-dong, Yuseong-gu, Daejeon 305-333, Korea.
Abstract:
Insulinoma-associated protein-2 (IA-2) is a major autoantigen in type 1 diabetes that occurs through autoimmune-mediated beta-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 beta-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.
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