The crystal structure of human receptor protein tyrosine phosphatase κ phosphatase domain 1

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. RPTPκ is a member of the R2A/IIb subfamily of RPTPs along with RPTPμ, RPTPρ, and RPTPλ. Here, we have determined the crystal structure of catalytically active, monomeric D1 domain of RPTPκ at 1.9 A. Structural comparison with other PTP family members indicates an overall classical PTP architecture of twisted mixed β-sheets flanked by α-helices, in which the catalytically important WPD loop is in an unhindered open conformation. Though the residues forming the dimeric interface in the RPTPμ structure are all conserved, they are not involved in the protein–protein interaction in RPTPκ. The N-terminal β-strand, formed by βx association with βy, is conserved only in RPTPs but not in cytosolic PTPs, and this feature is conserved in the RPTPκ structure forming a β-strand. Analytical ultracentrifugation studies show that the presence of reducing agents and higher ionic strength are necessary to maintain RPTPκ as a monomer. In this family the crystal structure of catalytically active RPTPμ 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 RPTPκ is monomeric in solution and crystal structure.