PDBsum entry 2v5y

Hydrolase

PDB id: 2v5y

Contents

Protein chain

564 a.a. *

Ligands

NAG ×7

Metals

_NA ×2

* Residue conservation analysis

PDB id:

2v5y

Name:

Hydrolase

Title:

Crystal structure of the receptor protein tyrosine phosphatase mu ectodomain

Structure:

Receptor-type tyrosine-protein phosphatase mu. Chain: a. Fragment: extracellular region, residues 21-742. Synonym: protein-tyrosine phosphatase mu, r-ptp-mu. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: lung. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek-293s gnti-.

Resolution:

3.10Å R-factor: 0.246 R-free: 0.320

Authors:

A.R.Aricescu,C.Siebold,K.Choudhuri,V.T.Chang,W.Lu,S.J.Davis,P.A.Van Der Merwe,E.Y.Jones

Key ref:

A.R.Aricescu et al. (2007). Structure of a tyrosine phosphatase adhesive interaction reveals a spacer-clamp mechanism. Science, 317, 1217-1220. PubMed id: 17761881 DOI: 10.1126/science.1144646

Date:

11-Jul-07 Release date: 11-Sep-07

Protein chain

P28827  (PTPRM_HUMAN) -  Receptor-type tyrosine-protein phosphatase mu from Homo sapiens

Seq: 1452 a.a.

Struc: 564 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1126/science.1144646

Science 317:1217-1220 (2007)

PubMed id: 17761881

Structure of a tyrosine phosphatase adhesive interaction reveals a spacer-clamp mechanism.

A.R.Aricescu, C.Siebold, K.Choudhuri, V.T.Chang, W.Lu, S.J.Davis, P.A.van der Merwe, E.Y.Jones.

ABSTRACT

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.

Selected figure(s)

Figure 2.
Fig. 2. eRPTPµ dimerization. (A) Ribbon diagram of the eRPTPµ dimer. The solvent-accessible surface is drawn in light gray, and the domains appear in blue (MAM), magenta (Ig), slate (FN1), yellow (FN2), green (FN3), and gray (FN4). The asterisk marks the crystallographic twofold axis. (B) Electrostatic properties. One monomer is shown as a solvent-accessible surface colored by electrostatic potential contoured at ±10 kT (red, acidic; blue, basic), and the other monomer is shown as a black ribbon. (C) The dimer interface. MAM and Ig domains of one molecule interact with FN1 and FN2 domains of another molecule. Domains are colored as in (A). Residues involved in dimer interactions are drawn in stick representation (oxygen, red; nitrogen, blue). Potential hydrophilic interactions are marked as gray dotted lines. Asterisks mark residues targeted for mutagenesis. (D) Hydrophobic interactions. Color coding is as in (C), and the N92-linked sugar is colored in green and forms stacking interactions with the indole ring of W151. (E) Cell adhesion assays. Non adherent insect Sf9 cells were infected with baculovirus constructs expressing either enhanced green fluorescent protein (EGFP) alone or RPTPµ-EGFP fusion constructs, wild type and mutant, and observed by phase contrast (top row) and fluorescence (bottom row) microscopy. Formation of aggregates indicates RPTPµ ectodomain adhesive function (8).

Figure 4.
Fig. 4. Model of adhesion-regulated RPTPµ signaling. Cadherins [ectodomains shown in orange, PDB entry 1L3W (29)] establish intercellular contacts via trans interactions, as well as cis interactions (black arrow) (2, 29). RPTPµ (shown in blue) trans interactions are pH sensitive (8, 18), which is consistent with the polar nature of the interface, and therefore cannot form at the low pH of the secretory pathway. Cell surface RPTPµ molecules rapidly recirculate, unless there is an appropriate recognition match (5). Trans RPTPµ dimerization may be complemented by weak interactions in cis (black arrow and question mark) (8, 15). RPTPµ can stabilize the cadherin-catenin complex [drawn schematically: -catenin (yellow circles), ß-catenin (light green ovals), and p120-catenin (dark green ovals)] by dephosphorylation (3)(red arrows). Type IIB RPTPs are processed in multiple proteolytic steps (5, 13, 14). Protein convertases (in the trans-Golgi network) nick the FN4 domain (13, 14), potentially contributing flexibility. ADAM 10 cleaves close to the membrane (thick gray lines), causing the shedding of RPTPµ (5, 14) and cadherin (36) ectodomains. Subsequent -secretase–dependent intramembrane cleavage releases the RPTPµ intracellular region (blue ovals) (14). The cadherin and RPTPµ ectodomains (crystal structures drawn to the same scale) are shown perpendicular to the cell surface to simplify the figure. EM analysis of adherens junctions and desmosomes has revealed the possibility of non-orthogonal orientations with respect to the membrane surface [with variable tilt angles (28, 31)], but it is not clear to what extent this is caused by sample preparation procedures or flexibility of the juxtamembrane regions.

The above figures are reprinted by permission from the AAAs: Science (2007, 317, 1217-1220) copyright 2007.

Figures were selected by an automated process.