2N6F

Structure of Pleiotrophin

2N6F の概要

• エントリーDOI: 10.2210/pdb2n6f/pdb
• NMR情報: BMRB: 25762
• 分子名称: Pleiotrophin (1 entity in total)
• 機能のキーワード: cytokine, glycosaminoglycan-binding protein, mitogen, angiogenesis, heparin-binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P21246
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15346.93

構造登録者

Ryan, E.O.,Shen, D.,Wang, X. (登録日: 2015-08-20, 公開日: 2016-04-20, 最終更新日: 2024-11-20)

主引用文献

Ryan, E.,Shen, D.,Wang, X.
Structural studies reveal an important role for the pleiotrophin C-terminus in mediating interactions with chondroitin sulfate.
Febs J., 283:1488-1503, 2016

PubMed 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-terminal domain and hinge of PTN make up the major CS-binding site in PTN, and that removal of the C-terminal tail weakened the affinity of the site for CSA but not for other high sulfation density CS.

PubMed: 26896299
DOI: 10.1111/febs.13686

実験手法

SOLUTION NMR