Structure of a tyrosine phosphatase adhesive interaction reveals a spacer-clamp mechanism
Aricescu AR, Siebold C, Choudhuri K, Chang VT, Lu W, Davis SJ, van der Merwe PA, Jones EY. (2007), Science. 317, 1217-20
Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. Human RPTPmu 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 RPTPmu 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 RPTPmu ectodomain acts as a distance gauge and plays a key regulatory function, locking the phosphatase to its appropriate functional location.
Key figure: Structure of the eRPTPμ monomer
(A) Ribbon diagram of eRPTPμ, in rainbow coloring (from N terminus in blue to C terminus in red). Sugars are depicted as slate-colored spheres. Modeled parts of the FN4 domain are colored in gray (but are not included in the structure refinement). Domains are indicated schematically at the left of the panel and, in RPTPμ, the ectodomain is followed by a transmembrane helix and two intracellular phosphatase domains. (B) Surface representation of eRPTPμ. Coloring is by residue conservation, based on an alignment of 23 sequences (shown in fig. S3A). (C to E) Close-up views of boxed interdomain junctions from (B). The Ig (magenta), FN1 (slate), FN2 (yellow), and FN3 (green) domains are shown as coils. Residues (35) involved in domain-domain interactions are drawn in stick representation (oxygen, red; nitrogen, blue; sulfur, lime). Potential hydrophilic interactions are marked as gray dotted lines.