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PDBsum entry 3n4w
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References listed in PDB file
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Key reference
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Title
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Structure of the mature ectodomain of the human receptor-Type protein-Tyrosine phosphatase ia-2.
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Authors
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M.E.Primo,
S.Klinke,
M.P.Sica,
F.A.Goldbaum,
J.Jakoncic,
E.Poskus,
M.R.Ermácora.
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Ref.
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J Biol Chem, 2008,
283,
4674-4681.
[DOI no: ]
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PubMed id
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Abstract
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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. A concerted 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 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.
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Figure 1.
FIGURE 1. Three-dimensional structure of meIA-2. a,
asymmetric unit. b, a second dimerization interface linking the
asymmetric unit in chains with antiparallel, two-fold screw axes
along unit cell c axis. c, diagram of the fold. Calcium ions are
shown as pinkish-purple spheres. d, sequence of meIA-2. Arrows
indicate the sites of spontaneous hydrolysis observed upon
incubation at 20 °C. The crystallographic molecules comprise
residues 21–109 of one monomer and 20–110 of the other.
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Figure 2.
FIGURE 2. Backbone superimposition of meIA-2 (in red) and
SEA domains of mucins (blue). Left, MUC1 (2acm.pdb (36)); right,
MUC16 (1ivz.pdb (37)).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
4674-4681)
copyright 2008.
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Secondary reference #1
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Title
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Structure of the mature ectodomain of the human receptor-Type protein-Tyrosine phosphatase ia-2.
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|
|
Authors
|
|
M.E.Primo,
S.Klinke,
M.P.Sica,
F.A.Goldbaum,
J.Jakoncic,
E.Poskus,
M.R.Ermácora.
|
|
|
Ref.
|
|
J Biol Chem, 2008,
283,
4674-4681.
[DOI no: ]
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PubMed id
|
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Figure 1.
FIGURE 1. Three-dimensional structure of meIA-2. a,
asymmetric unit. b, a second dimerization interface linking the
asymmetric unit in chains with antiparallel, two-fold screw axes
along unit cell c axis. c, diagram of the fold. Calcium ions are
shown as pinkish-purple spheres. d, sequence of meIA-2. Arrows
indicate the sites of spontaneous hydrolysis observed upon
incubation at 20 °C. The crystallographic molecules comprise
residues 21–109 of one monomer and 20–110 of the other.
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Figure 2.
FIGURE 2. Backbone superimposition of meIA-2 (in red) and
SEA domains of mucins (blue). Left, MUC1 (2acm.pdb (36)); right,
MUC16 (1ivz.pdb (37)).
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The above figures are
reproduced from the cited reference
with permission from the ASBMB
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