2yd4

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Crystal structure of the N-terminal Ig1-2 module of Chicken Receptor Protein Tyrosine Phosphatase Sigma

Structural highlights

2yd4 is a 1 chain structure with sequence from Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.65Å
Ligands:CL, PEG, PGE, SO4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PTPRS_CHICK Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycans (PubMed:11865065, PubMed:17178832). Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth (By similarity). Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection (PubMed:17967490). Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb. Functions as tyrosine phosphatase (PubMed:17967490). Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3 (PubMed:17967490). Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases. Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta (By similarity).[UniProtKB:B0V2N1][1] [2] [3]

Publication Abstract from PubMed

Heparan and chondroitin sulfate proteoglycans (HSPGs and CSPGs) regulate numerous cell surface signaling events, with typically opposite effects on cell function. CSPGs inhibit nerve regeneration through receptor protein tyrosine phosphatase sigma (RPTPsigma). Here, we report that RPTPsigma acts bimodally in sensory neuron extension, mediating CSPG inhibition and HSPG growth promotion. Crystallographic analyses of a shared HSPG-CSPG binding site reveal a conformational plasticity that can accommodate diverse glycosaminoglycans with comparable affinities. Heparan sulfate and analogues induced RPTPsigma ectodomain oligomerization in solution, which chondroitin sulfate inhibited. RPTPsigma and HSPGs colocalize in puncta on sensory neurons in culture, whereas CSPGs occupy the extracellular matrix. These results lead to a model where proteoglycans can exert opposing effects on neuronal extension by competing to control the oligomerization of a common receptor.

Proteoglycan-Specific Molecular Switch for RPTP{sigma} Clustering and Neuronal Extension.,Coles CH, Shen Y, Tenney AP, Siebold C, Sutton GC, Lu W, Gallagher JT, Jones EY, Flanagan JG, Aricescu AR Science. 2011 Mar 31. PMID:21454754[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
76 reviews cite this structure
Demystifying heparan sulfate-protein interactions.
Xu et al. (2014)
75 more
125 other articles
No citations found

See Also

References

  1. ↑ Aricescu AR, McKinnell IW, Halfter W, Stoker AW. Heparan sulfate proteoglycans are ligands for receptor protein tyrosine phosphatase sigma. Mol Cell Biol. 2002 Mar;22(6):1881-92. PMID:11865065 doi:10.1128/MCB.22.6.1881-1892.2002
  2. ↑ Lee S, Faux C, Nixon J, Alete D, Chilton J, Hawadle M, Stoker AW. Dimerization of protein tyrosine phosphatase sigma governs both ligand binding and isoform specificity. Mol Cell Biol. 2007 Mar;27(5):1795-808. PMID:17178832 doi:10.1128/MCB.00535-06
  3. ↑ Faux C, Hawadle M, Nixon J, Wallace A, Lee S, Murray S, Stoker A. PTPsigma binds and dephosphorylates neurotrophin receptors and can suppress NGF-dependent neurite outgrowth from sensory neurons. Biochim Biophys Acta. 2007 Nov;1773(11):1689-700. PMID:17967490 doi:10.1016/j.bbamcr.2007.06.008
  4. ↑ Coles CH, Shen Y, Tenney AP, Siebold C, Sutton GC, Lu W, Gallagher JT, Jones EY, Flanagan JG, Aricescu AR. Proteoglycan-Specific Molecular Switch for RPTP{sigma} Clustering and Neuronal Extension. Science. 2011 Mar 31. PMID:21454754 doi:10.1126/science.1200840

Contents


PDB ID 2yd4

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