2MVK

Solution structure of phosphorylated cytosolic part of Trop2

2MVK の概要

• エントリーDOI: 10.2210/pdb2mvk/pdb
• NMR情報: BMRB: 25273
• 分子名称: Tumor-associated calcium signal transducer 2 (1 entity in total)
• 機能のキーワード: phospotilated cytosolic part of trop2, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P09758
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3176.63

構造登録者

Ilc, G.,Plavec, J.,Vidmar, T.,Pavsic, M.,Lenarcic, B. (登録日: 2014-10-08, 公開日: 2015-05-06, 最終更新日: 2024-11-27)

主引用文献

Pavsic, M.,Ilc, G.,Vidmar, T.,Plavec, J.,Lenarcic, B.
The cytosolic tail of the tumor marker protein Trop2--a structural switch triggered by phosphorylation.
Sci Rep, 5:10324-10324, 2015

PubMed Abstract: Trop2 is a transmembrane signaling glycoprotein upregulated in stem and carcinoma cells. Proliferation-enhancing signaling involves regulated intramembrane proteolytic release of a short cytoplasmic fragment, which is later engaged in a cytosolic signaling complex. We propose that Trop2 function is modulated by phosphorylation of a specific serine residue within this cytosolic region (Ser303), and by proximity effects exerted on the cytosolic tail by Trop2 dimerization. Structural characterization of both the transmembrane (Trop2TM) and cytosolic regions (Trop2IC) support this hypothesis, and shows that the central region of Trop2IC forms an α-helix. Comparison of NMR structures of non-phosphorylated and phosphorylated forms suggest that phosphorylation of Trop2IC triggers salt bridge reshuffling, resulting in significant conformational changes including ordering of the C-terminal tail. In addition, we demonstrate that the cytosolic regions of two Trop2 subunits can be brought into close proximity via transmembrane part dimerization. Finally, we show that Ser303-phosphorylation significantly affects the structure and accessibility of functionally important regions of the cytosolic tail. These observed structural features of Trop2 at the membrane-cytosol interface could be important for regulation of Trop2 signaling activity.

PubMed: 25981199
DOI: 10.1038/srep10324

実験手法

SOLUTION NMR