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Title: Protein-Protein Interactions in Crystals of the Human Receptor-Type Protein Tyrosine Phosphatase ICA512 Ectodomain

Abstract

ICA512 (or IA-2) is a transmembrane protein-tyrosine phosphatase located in secretory granules of neuroendocrine cells. Initially, it was identified as one of the main antigens of autoimmune diabetes. Later, it was found that during insulin secretion, the cytoplasmic domain of ICA512 is cleaved and relocated to the nucleus, where it stimulates the transcription of the insulin gene. The role of the other parts of the receptor in insulin secretion is yet to be unveiled. The structures of the intracellular pseudocatalytic and mature extracellular domains are known, but the transmembrane domain and several intracellular and extracellular parts of the receptor are poorly characterized. Moreover the overall structure of the receptor remains to be established. We started to address this issue studying by X-ray crystallography the structure of the mature ectodomain of ICA512 (ME ICA512) and variants thereof. The variants and crystallization conditions were chosen with the purpose of exploring putative association interfaces, metal binding sites and all other structural details that might help, in subsequent works, to build a model of the entire receptor. Several structural features were clarified and three main different association modes of ME ICA512 were identified. The results provide essential pieces of information for the design ofmore » new experiments aimed to assess the structure in vivo.« less

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
BROOKHAVEN NATIONAL LABORATORY (BNL)
Sponsoring Org.:
USDOE SC OFFICE OF SCIENCE (SC)
OSTI Identifier:
1041601
Report Number(s):
BNL-96735-2012-JA
R&D Project: LS01; TRN: US201212%%19
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
PLoS One
Additional Journal Information:
Journal Volume: 6; Journal Issue: 9
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ANTIGENS; CRYSTALLIZATION; CRYSTALLOGRAPHY; DESIGN; IN VIVO; INSULIN; INTERACTIONS; PHOSPHATASES; PROTEINS; SECRETION; TRANSCRIPTION; TYROSINE; protein crystallofraphy; phosphatase; dimerization

Citation Formats

Primo M. E., Jakoncic J., Noguera M.E., Risso V.A., Sosa L., Sica M.P., Solimena M., and Poskus E. and Ermacora M. Protein-Protein Interactions in Crystals of the Human Receptor-Type Protein Tyrosine Phosphatase ICA512 Ectodomain. United States: N. p., 2011. Web. doi:10.1371/journal.pone.0024191.
Primo M. E., Jakoncic J., Noguera M.E., Risso V.A., Sosa L., Sica M.P., Solimena M., & Poskus E. and Ermacora M. Protein-Protein Interactions in Crystals of the Human Receptor-Type Protein Tyrosine Phosphatase ICA512 Ectodomain. United States. doi:10.1371/journal.pone.0024191.
Primo M. E., Jakoncic J., Noguera M.E., Risso V.A., Sosa L., Sica M.P., Solimena M., and Poskus E. and Ermacora M. Thu . "Protein-Protein Interactions in Crystals of the Human Receptor-Type Protein Tyrosine Phosphatase ICA512 Ectodomain". United States. doi:10.1371/journal.pone.0024191.
@article{osti_1041601,
title = {Protein-Protein Interactions in Crystals of the Human Receptor-Type Protein Tyrosine Phosphatase ICA512 Ectodomain},
author = {Primo M. E. and Jakoncic J. and Noguera M.E. and Risso V.A. and Sosa L. and Sica M.P. and Solimena M. and Poskus E. and Ermacora M.},
abstractNote = {ICA512 (or IA-2) is a transmembrane protein-tyrosine phosphatase located in secretory granules of neuroendocrine cells. Initially, it was identified as one of the main antigens of autoimmune diabetes. Later, it was found that during insulin secretion, the cytoplasmic domain of ICA512 is cleaved and relocated to the nucleus, where it stimulates the transcription of the insulin gene. The role of the other parts of the receptor in insulin secretion is yet to be unveiled. The structures of the intracellular pseudocatalytic and mature extracellular domains are known, but the transmembrane domain and several intracellular and extracellular parts of the receptor are poorly characterized. Moreover the overall structure of the receptor remains to be established. We started to address this issue studying by X-ray crystallography the structure of the mature ectodomain of ICA512 (ME ICA512) and variants thereof. The variants and crystallization conditions were chosen with the purpose of exploring putative association interfaces, metal binding sites and all other structural details that might help, in subsequent works, to build a model of the entire receptor. Several structural features were clarified and three main different association modes of ME ICA512 were identified. The results provide essential pieces of information for the design of new experiments aimed to assess the structure in vivo.},
doi = {10.1371/journal.pone.0024191},
journal = {PLoS One},
number = 9,
volume = 6,
place = {United States},
year = {2011},
month = {9}
}