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PDBsum entry 2v5y

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protein ligands metals links
Hydrolase PDB id
2v5y
Jmol
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    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28827  (PTPRM_HUMAN) -  Receptor-type tyrosine-protein phosphatase mu
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1452 a.a.
564 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.3.48  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
=
protein tyrosine
Bound ligand (Het Group name = NAG)
matches with 47.62% similarity
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 

 

 
    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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21517784 A.Scott, and Z.Wang (2011).
Tumour suppressor function of protein tyrosine phosphatase receptor-T.
  Biosci Rep, 31, 303-307.  
19936768 A.C.Navis, M.van den Eijnden, J.T.Schepens, R.Hooft van Huijsduijnen, P.Wesseling, and W.J.Hendriks (2010).
Protein tyrosine phosphatases in glioma biology.
  Acta Neuropathol, 119, 157-175.  
  20521994 S.Becka, P.Zhang, S.E.Craig, D.T.Lodowski, Z.Wang, and S.M.Brady-Kalnay (2010).
Characterization of the adhesive properties of the type IIb subfamily receptor protein tyrosine phosphatases.
  Cell Commun Adhes, 17, 34-47.  
20133774 S.Bouyain, and D.J.Watkins (2010).
The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules.
  Proc Natl Acad Sci U S A, 107, 2443-2448.
PDB codes: 3jxa 3jxf 3jxg 3jxh 3kld
  20360941 S.M.Burden-Gulley, T.J.Gates, A.M.Burgoyne, J.L.Cutter, D.T.Lodowski, S.Robinson, A.E.Sloan, R.H.Miller, J.P.Basilion, and S.M.Brady-Kalnay (2010).
A novel molecular diagnostic of glioblastomas: detection of an extracellular fragment of protein tyrosine phosphatase mu.
  Neoplasia, 12, 305-316.  
20659327 S.N.Kariuki, B.S.Franek, A.A.Kumar, J.Arrington, R.A.Mikolaitis, T.O.Utset, M.Jolly, M.K.Crow, A.D.Skol, and T.B.Niewold (2010).
Trait-stratified genome-wide association study identifies novel and diverse genetic associations with serologic and cytokine phenotypes in systemic lupus erythematosus.
  Arthritis Res Ther, 12, R151.  
19167335 A.J.Barr, E.Ugochukwu, W.H.Lee, O.N.King, P.Filippakopoulos, I.Alfano, P.Savitsky, N.A.Burgess-Brown, S.Müller, and S.Knapp (2009).
Large-scale structural analysis of the classical human protein tyrosine phosphatome.
  Cell, 136, 352-363.
PDB codes: 2ahs 2b49 2cfv 2cjz 2gjt 2h4v 2i75 2jjd 2nlk 2nz6 2oc3 2ooq 2p6x 2pa5 2qep 3b7o
  19377077 A.J.Ramsay, J.D.Hooper, A.R.Folgueras, G.Velasco, and C.López-Otín (2009).
Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis.
  Haematologica, 94, 840-849.  
19633684 D.C.Stylianou, A.Auf der Maur, D.P.Kodack, R.T.Henke, S.Hohn, J.A.Toretsky, A.T.Riegel, and A.Wellstein (2009).
Effect of single-chain antibody targeting of the ligand-binding domain in the anaplastic lymphoma kinase receptor.
  Oncogene, 28, 3296-3306.  
20230342 P.Zhang, S.Becka, S.E.Craig, D.T.Lodowski, S.M.Brady-Kalnay, and Z.Wang (2009).
Cancer-derived mutations in the fibronectin III repeats of PTPRT/PTPrho inhibit cell-cell aggregation.
  Cell Commun Adhes, 16, 146-153.  
19816407 S.H.Lim, S.K.Kwon, M.K.Lee, J.Moon, D.G.Jeong, E.Park, S.J.Kim, B.C.Park, S.C.Lee, S.E.Ryu, D.Y.Yu, B.H.Chung, E.Kim, P.K.Myung, and J.R.Lee (2009).
Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn.
  EMBO J, 28, 3564-3578.  
19383447 V.Maruthamuthu, K.Schulten, and D.Leckband (2009).
Elasticity and rupture of a multi-domain neural cell adhesion molecule complex.
  Biophys J, 96, 3005-3014.  
18422654 A.Groen, J.Overvoorde, T.van der Wijk, and J.den Hertog (2008).
Redox regulation of dimerization of the receptor protein-tyrosine phosphatases RPTPalpha, LAR, RPTPmu and CD45.
  FEBS J, 275, 2597-2604.  
18564362 A.Nishimura, T.Takano, T.Mizuguchi, H.Saitsu, Y.Takeuchi, and N.Matsumoto (2008).
CDKL5 disruption by t(X;18) in a girl with West syndrome.
  Clin Genet, 74, 288-290.  
19074898 D.A.Solomon, J.S.Kim, J.C.Cronin, Z.Sibenaller, T.Ryken, S.A.Rosenberg, H.Ressom, W.Jean, D.Bigner, H.Yan, Y.Samuels, and T.Waldman (2008).
Mutational inactivation of PTPRD in glioblastoma multiforme and malignant melanoma.
  Cancer Res, 68, 10300-10306.  
18644975 J.Yu, S.Becka, P.Zhang, X.Zhang, S.M.Brady-Kalnay, and Z.Wang (2008).
Tumor-derived extracellular mutations of PTPRT /PTPrho are defective in cell adhesion.
  Mol Cancer Res, 6, 1106-1113.  
18298791 J.den Hertog, A.Ostman, and F.D.Böhmer (2008).
Protein tyrosine phosphatases: regulatory mechanisms.
  FEBS J, 275, 831-847.  
18298793 L.Tabernero, A.R.Aricescu, E.Y.Jones, and S.E.Szedlacsek (2008).
Protein tyrosine phosphatases: structure-function relationships.
  FEBS J, 275, 867-882.  
18823116 W.Zhao, D.E.Moilanen, E.E.Fenn, and M.D.Fayer (2008).
Water at the surfaces of aligned phospholipid multibilayer model membranes probed with ultrafast vibrational spectroscopy.
  J Am Chem Soc, 130, 13927-13937.  
17935964 A.R.Aricescu, and E.Y.Jones (2007).
Immunoglobulin superfamily cell adhesion molecules: zippers and signals.
  Curr Opin Cell Biol, 19, 543-550.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.