The crystal structure of domain 1 of receptor protein-tyrosine phosphatase mu

Receptor like protein-tyrosine phosphatases (RPTPs) play important roles in regulating intracellular processes, We have been investigating the regulation and function of RPTP mu, a receptor-like PTP related to the Ig superfamily of cell adhesion molecules, Recently, the crystal structure of a dimer of the membrane proximal domain of RPTP alpha (RPTP alpha D1) was described (Bilwes, A. M., den Hertog, J., Hunter, T., and Noel J. P. (1996) Nature 382, 555-559). Within this crystal structure, the catalytic site of each subunit of the dimer is sterically blocked by the insertion of the N-terminal helix-turn-helix segment of the dyad-related monomer, It was proposed that dimerization would lead to inhibition of catalytic activity and may provide a paradigm for the regulation of the RPTP family, We have determined the crystal structure, to 2.3 Angstrom resolution, of RPTP mu D1, which shares 46% sequence identity with that of RPTP alpha D1, Although the tertiary structures of RPTP alpha D1 and RPTP mu D1 are very similar, with a root mean square deviation between equivalent C alpha atoms of 1.1 Angstrom, the quaternary structures of these two proteins are different, Neither the catalytic site nor the N-terminal helix-turn-helix segment of RPTP mu D1 participates in protein-protein interactions, The catalytic site of RPTP mu D1 is unhindered and adopts an open conformation similar to that of the cytosolic PTP, PTP1B (Barford, D., Flint, A. J., and Tonks, N. K. (1994) Science 263, 1397-1404), We propose that dimerization-induced modulation of RPTP activity may not be a general feature of this family of enzymes.