THE CRYSTAL-STRUCTURE OF DOMAIN-1 OF RECEPTOR PROTEIN-TYROSINE-PHOSPHATASE-MU

Receptor like protein-tyrosine phosphatases (RPTPs) play important rol es in regulating intracellular processes, We have been investigating t he regulation and function of RPTP mu, a receptor-like PTP related to the Ig superfamily of cell adhesion molecules, Recently, the crystal s tructure of a dimer of the membrane proximal domain of RPTP alpha (RPT P alpha D1) was described (Bilwes, A. M., den Hertog, J., Hunter, T., and Noel J. P. (1996) Nature 382, 555-559). Within this crystal struct ure, the catalytic site of each subunit of the dimer is sterically blo cked by the insertion of the N-terminal helix-turn-helix segment of th e dyad-related monomer, It was proposed that dimerization would lead t o inhibition of catalytic activity and may provide a paradigm for the regulation of the RPTP family, We have determined the crystal structur e, to 2.3 Angstrom resolution, of RPTP mu D1, which shares 46% sequenc e identity with that of RPTP alpha D1, Although the tertiary structure s of RPTP alpha D1 and RPTP mu D1 are very similar, with a root mean s quare 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 o f 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-i nduced modulation of RPTP activity may not be a general feature of thi s family of enzymes.