Structural studies reveal an important role for the pleiotrophin C-terminus in mediating interactions with chondroitin sulfate

The FEBS Journal
Eathen RyanXu Wang

Abstract

Pleiotrophin (PTN) is a potent glycosaminoglycan-binding cytokine that is important in neural development, angiogenesis and tissue regeneration. Much of its activity is attributed to its interactions with the chondroitin sulfate (CS) proteoglycan, receptor type protein tyrosine phosphatase ζ (PTPRZ). However, there is little high resolution structural information on the interactions between PTN and CS, nor is it clear why the C-terminal tail of PTN is necessary for signaling through PTPRZ, even though it does not contribute to heparin binding. We determined the first structure of PTN and analyzed its interactions with CS. Our structure shows that PTN possesses large basic surfaces on both of its structured domains and also that residues in the hinge segment connecting the domains have significant contacts with the C-terminal domain. Our analysis of PTN-CS interactions showed that the C-terminal tail of PTN is essential for maintaining stable interactions with chondroitin sulfate A, the type of CS commonly found on PTPRZ. These results offer the first possible explanation of why truncated PTN missing the C-terminal tail is unable to signal through PTPRZ. NMR analysis of the interactions of PTN with CS revealed that the C-termina...Continue Reading

References

Jun 1, 1992·Protein Science : a Publication of the Protein Society·S G HybertsG Wagner
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Jul 4, 1997·The Journal of Biological Chemistry·N ZhangT F Deuel
Jan 31, 1998·The EMBO Journal·W IwasakiF Inagaki
Dec 6, 1997·International Journal of Cancer. Journal International Du Cancer·R JägerG Zugmaier
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Dec 2, 2000·Journal of Biomolecular NMR·D Sharma, K Rajarathnam
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Nov 8, 2002·Journal of Neurochemistry·Rolf Mentlein, Janka Held-Feindt
Feb 5, 2003·Journal of Magnetic Resonance·Charles D SchwietersG Marius Clore
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexander W Schüttelkopf, Daan M F van Aalten
Feb 3, 2005·Neurologia Medico-chirurgica·Lei ZhangHirofumi Naganuma
May 24, 2005·The Journal of Biological Chemistry·Kan V LuPaul S Mischel
Jun 1, 2005·The Prostate·Maria HatziapostolouEvangelia Papadimitriou
Apr 9, 2008·Current Opinion in Hematology·Pablo Perez-PineraThomas F Deuel
Sep 2, 2008·Cancer Research·Kazuki N SugaharaMasayuki Miyasaka
Jan 15, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Constantinos MikelisEvangelia Papadimitriou
Jun 25, 2009·Current Medicinal Chemistry·Gonzalo Herradón, Laura Ezquerra
Jul 2, 2009·Molecular & Cellular Proteomics : MCP·Alessandro OriDavid G Fernig
Feb 24, 2011·Journal of Cellular Biochemistry·Constantinos MikelisEvangelia Papadimitriou
Jun 9, 2011·Molecular Neurodegeneration·Irene Re TaraviniOscar S Gershanik
Dec 6, 2011·Carbohydrate Polymers·Chao CaiFuming Zhang

❮ Previous
Next ❯

Citations

Oct 25, 2016·Biochimica Et Biophysica Acta·Evangelia PapadimitriouDimitris Beis
Apr 2, 2019·The FEBS Journal·Pinelopi KastanaEvangelia Papadimitriou
May 21, 2019·Critical Reviews in Biochemistry and Molecular Biology·Surbhi Sharma, Martin R Schiller
Dec 18, 2018·European Journal of Medicinal Chemistry·Wang YaoZhongjun Li
Apr 3, 2021·Frontiers in Molecular Biosciences·Changkai Bu, Lan Jin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.