IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
artículos
Título:
Structure of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase IA-2
Autor/es:
PRIMO, M.E., KLINKE, S., SICA, M.P., GOLDBAUM, F.A., JAKONCIC, J., POSKUS, E., ERMÁCORA M.R.
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
ASBMB
Referencias:
Año: 2008 vol. 283 p. 4674 - 4681
ISSN:
0021-9258
Resumen:
IA-2 (insulinoma-associated protein 2) is a protein-tyrosine
phosphatase receptor located in secretory granules of neuroendocrine
cells. Initially, it attracted attention due to its involvement in
the autoimmune response associated to diabetes. Later it was
found that upon exocytosis, the cytoplasmic domain of IA-2 is
cleaved and relocated to the nucleus, where it enhances the transcription
of the insulin gene.Aconcerted functioning of the whole
receptor is to be expected. However, very little is known about the
structure and function of the transmembrane and extracellular
domains of IA-2. To address this issue, we solved the x-ray structure
of the mature ectodomain of IA-2 (meIA-2) to 1.30A¢ª resolution.
The fold of meIA-2 is related to the SEA (sea urchin sperm
protein, enterokinase, agrin)) domains of mucins, suggesting its
participation in adhesive contacts to the extracellular matrix and
providing clues on how this kind of molecule may associate and
form homo- and heterodimers. Moreover, we discovered that
meIA-2 is self-proteolyzed in vitro by reactive oxygen species, suggesting
the possibility of a new shedding mechanism that might be
significant in normal function or pathological processes. Knowledge
of meIA-2 structure should facilitate the search of its possible
ligands and molecular interactions.