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

• Published in: Science (American Association for the Advancement of Science) Vol. 317; no. 5842; pp. 1217 - 1220
• Main Authors: Aricescu, A. Radu, Siebold, Christian, Choudhuri, Kaushik, Chang, Veronica T, Lu, Weixian, Davis, Simon J, van der Merwe, P. Anton, Jones, E. Yvonne
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 31.08.2007; The American Association for the Advancement of Science
• Subjects: Adherens Junctions - chemistry; Adherens Junctions - physiology; Adherens Junctions - ultrastructure; Adhesives; Amino Acid Sequence; Biological and medical sciences; Cadherins; Cell Adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - metabolism; Cell Membrane - chemistry; Cell Membrane - enzymology; Conserved Sequence; Crystal structure; Crystalline structure; Dimerization; Dimers; Enzymes; Fibronectins - chemistry; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen Bonding; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Immunoglobulins - chemistry; Models, Molecular; Molecular biophysics; Molecular interactions; Molecular Sequence Data; Molecules; Monomers; Mutagenesis, Site-Directed; Oncology; Phosphatases; Protein Structure, Tertiary; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - metabolism; Proteins; Receptor-Like Protein Tyrosine Phosphatases, Class 2; Structure in molecular biology; Trans golgi network; Tyrosine; Enzyme; Cell adhesion; Phosphoric monoester hydrolases; Hydrolases; Molecular interaction; Esterases; Protein-tyrosine-phosphatase; Crystalline structure
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1144646

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.