2YD6

Crystal structure of the N-terminal Ig1-2 module of Human Receptor Protein Tyrosine Phosphatase Delta

Summary for 2YD6

• Entry DOI: 10.2210/pdb2yd6/pdb
• Related: 2YD1 2YD2 2YD3 2YD4 2YD5 2YD7 2YD8 2YD9
• Descriptor: PTPRD PROTEIN, CHLORIDE ION, CITRATE ANION, ... (4 entities in total)
• Functional Keywords: hydrolase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 23704.75

Authors

Coles, C.H.,Shen, Y.,Tenney, A.P.,Siebold, C.,Sutton, G.C.,Lu, W.,Gallagher, J.T.,Jones, E.Y.,Flanagan, J.G.,Aricescu, A.R. (deposition date: 2011-03-17, release date: 2011-04-13, Last modification date: 2024-10-23)

Primary citation

Coles, C.H.,Shen, Y.,Tenney, A.P.,Siebold, C.,Sutton, G.C.,Lu, W.,Gallagher, J.T.,Jones, E.Y.,Flanagan, J.G.,Aricescu, A.R.
Proteoglycan-Specific Molecular Switch for Rptp Sigma Clustering and Neuronal Extension.
Science, 332:484-, 2011

PubMed Abstract: Heparan and chondroitin sulfate proteoglycans (HSPGs and CSPGs, respectively) regulate numerous cell surface signaling events, with typically opposite effects on cell function. CSPGs inhibit nerve regeneration through receptor protein tyrosine phosphatase sigma (RPTPσ). Here we report that RPTPσ 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 analogs induced RPTPσ ectodomain oligomerization in solution, which was inhibited by chondroitin sulfate. RPTPσ 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.

PubMed: 21454754
DOI: 10.1126/SCIENCE.1200840

Experimental method

X-RAY DIFFRACTION (1.35 Å)