2A3K: Crystal Structure Of The Human Protein Tyrosine Phosphatase, Ptpn7 (Heptp, Hematopoietic Protein Tyrosine Phosphatase)

The receptor-type protein tyrosine phosphatases (RPTPs) are integral membrane proteins composed of extracellular adhesion molecule-like domains, a single transmembrane domain, and a cytoplasmic domain. The cytoplasmic domain consists of tandem PTP domains, of which the D1 domain is enzymatically active. RPTPkappa is a member of the R2A/IIb subfamily of RPTPs along with RPTPmu, RPTPrho, and RPTPlambda. Here, we have determined the crystal structure of catalytically active, monomeric D1 domain of RPTPkappa at 1.9 A. Structural comparison with other PTP family members indicates an overall classical PTP architecture of twisted mixed beta-sheets flanked by alpha-helices, in which the catalytically important WPD loop is in an unhindered open conformation. Though the residues forming the dimeric interface in the RPTPmu structure are all conserved, they are not involved in the protein-protein interaction in RPTPkappa. The N-terminal beta-strand, formed by betax association with betay, is conserved only in RPTPs but not in cytosolic PTPs, and this feature is conserved in the RPTPkappa structure forming a beta-strand. Analytical ultracentrifugation studies show that the presence of reducing agents and higher ionic strength are necessary to maintain RPTPkappa as a monomer. In this family the crystal structure of catalytically active RPTPmu D1 was solved as a dimer, but the dimerization was proposed to be a consequence of crystallization since the protein was monomeric in solution. In agreement, we show that RPTPkappa is monomeric in solution and crystal structure.
PDB ID: 2A3KDownload
MMDB ID: 34373
PDB Deposition Date: 2005/6/24
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.55  Å
Source Organism:
Similar Structures:
Biological Unit for 2A3K: monomeric; determined by author
Molecular Components in 2A3K
Label Count Molecule
Protein (1 molecule)
Protein Tyrosine Phosphatase, Non-receptor Type 7 1
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

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