Structural studies reveal an important role for the pleiotrophin C-terminus in mediating interactions with chondroitin sulfate.
Structural studies reveal an important role for the pleiotrophin C-terminus in mediating interactions with chondroitin sulfate.
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DOI：
10.1111/febs.13686
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Ryan E;Shen D;Wang X
Pleiotrophin (PTN) is a potent glycosaminoglycan-binding cytokine 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 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 binding heparin. We determined the first structure of PTN and analyzed its interactions with CS. Our structure shows PTN possesses large basic surfaces on both of its structured domains and residues in the hinge segment connecting the domains have significant contacts with the C-terminal domain. Our analysis of PTN-CS interactions showed the C-terminal tail of PTN is essential for maintaining stable interactions with CSA, 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 PTN’s interactions 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 site’s affinity for CSA, but not for other high sulfation density CS.
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影响因子：
5.7
作者：
Deshauer, Courtney;Morgan, Ashli M.;Ryan, Eathen O.;Handel, Tracy M.;Prestegard, James H.;Wang, Xu
通讯作者：
Wang, Xu
影响因子：
4.1
作者：
Lim, Jackwee;Yao, Sheng;Yang, Daiwen
通讯作者：
Yang, Daiwen
影响因子：
4.8
作者：
Maeda, N;He, J;Yabe, T
通讯作者：
Yabe, T
影响因子：
4.8
作者：
Lu, KV;Jong, KA;Mischel, PS
通讯作者：
Mischel, PS
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL