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Science 31 August 2007:
Vol. 317. no. 5842, pp. 1217 - 1220
DOI: 10.1126/science.1144646
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Reports

Structure of a Tyrosine Phosphatase Adhesive Interaction Reveals a Spacer-Clamp Mechanism

A. Radu Aricescu,1* Christian Siebold,1* Kaushik Choudhuri,2 Veronica T. Chang,3 Weixian Lu,1 Simon J. Davis,3 P. Anton van der Merwe,2 E. Yvonne Jones1{dagger}

Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. Human RPTPµ is a type IIB receptor protein tyrosine phosphatase that both forms an adhesive contact itself and is involved in regulating adhesion by dephosphorylating components of cadherin-catenin complexes. Here we describe a 3.1 angstrom crystal structure of the RPTPµ ectodomain that forms a homophilic trans (antiparallel) dimer with an extended and rigid architecture, matching the dimensions of adherens junctions. Cell surface expression of deletion constructs induces intercellular spacings that correlate with the ectodomain length. These data suggest that the RPTPµ ectodomain acts as a distance gauge and plays a key regulatory function, locking the phosphatase to its appropriate functional location.

1 Cancer Research UK Receptor Structure Research Group, University of Oxford, Henry Wellcome Building of Genomic Medicine, Division of Structural Biology, Roosevelt Drive, Oxford OX3 7BN, UK.
2 Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
3 Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: yvonne{at}strubi.ox.ac.uk

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Science. ISSN 0036-8075 (print), 1095-9203 (online)