The Crystal Structure of Domain 1 of Receptor Protein-tyrosine Phosphatase μ*
- From the ‡Laboratory of Molecular Biophysics, University of Oxford, Rex Richards Building, South Parks Road, Oxford OX1 3QU, United Kingdom and the ¶Cold Spring Harbor Laboratory, P. O. Box 100, Cold Spring Harbor, New York 11724
Abstract
Receptor-like protein-tyrosine phosphatases (RPTPs) play important roles in regulating intracellular processes. We have been investigating the regulation and function of RPTPμ, 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 RPTPα (RPTPα 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 Å resolution, of RPTPμ D1, which shares 46% sequence identity with that of RPTPα D1. Although the tertiary structures of RPTPα D1 and RPTPμ D1 are very similar, with a root mean square deviation between equivalent Cα atoms of 1.1 Å, the quaternary structures of these two proteins are different. Neither the catalytic site nor the N-terminal helix-turn-helix segment of RPTPμ D1 participates in protein-protein interactions. The catalytic site of RPTPμ 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.
Footnotes
-
↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The atomic coordinates and structure factors (PDB ID code 1rpm (coordinates); PDB ID code r1rpmsf (for structure factor)) have been deposited in the Protein Data Bank, Brookhaven National Laboratory, Upton, NY.
-
↵§ Supported by a European Union Training and Mobility of Researchers grant.
-
↵‖ Supported by National Institutes of Health Grant GM 55989.
-
↵** Supported by the Medical Research Council and the Wellcome Trust. To whom correspondence should be addressed. Tel.: 44-1865-275377; Fax: 44-1865-275182; E-mail: davidb{at}biop.ox.ac.uk.
-
↵1 The abbreviations used are: PTP, protein-tyrosine phosphatases; RPTP, receptor protein-tyrosine phosphatase; D1, domain 1 (membrane proximal domain) of RPTPs; DTT, dithiothreitol; NCS, noncrystallographic symmetry.
-
↵2 D. Barford and N. Hanlon, unpublished data.
-
- Received July 8, 1997.
- Revision received September 3, 1997.
