PDBsum entry 3n4w

Transferase

PDB id: 3n4w

Contents

Protein chains

87 a.a. *

81 a.a. *

Metals

_CA

Waters ×141

* Residue conservation analysis

PDB id:

3n4w

Name:

Transferase

Title:

Crystal structure of an abridged ser to ala mutant of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase ica512/ia-2 at ph 7.5

Structure:

Receptor-type tyrosine-protein phosphatase-like n. Chain: a, b. Fragment: unp residues 470-558. Synonym: r-ptp-n, ptp ia-2, islet cell antigen 512, ica 512, islet cell autoantigen 3. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ica3, ica512, ptprn. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.45Å R-factor: 0.187 R-free: 0.227

Authors:

M.E.Primo,J.Jakoncic,E.Poskus,M.R.Ermacora

Key ref:

M.E.Primo et al. (2008). Structure of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase IA-2. J Biol Chem, 283, 4674-4681. PubMed id: 18048354 DOI: 10.1074/jbc.M708144200

Date:

23-May-10 Release date: 01-Dec-10

Protein chain

Q16849  (PTPRN_HUMAN) -  Receptor-type tyrosine-protein phosphatase-like N from Homo sapiens

Seq: 979 a.a.

Struc: 87 a.a.*

Protein chain

Q16849  (PTPRN_HUMAN) -  Receptor-type tyrosine-protein phosphatase-like N from Homo sapiens

Seq: 979 a.a.

Struc: 81 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1074/jbc.M708144200

J Biol Chem 283:4674-4681 (2008)

PubMed id: 18048354

Structure of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase IA-2.

M.E.Primo, S.Klinke, M.P.Sica, F.A.Goldbaum, J.Jakoncic, E.Poskus, M.R.Ermácora.

ABSTRACT

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.

Selected figure(s)

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.

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)).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 4674-4681) copyright 2008.

Figures were selected by the author.