2MS4

Cyclophilin a complexed with a fragment of crk-ii

2MS4 の概要

• エントリーDOI: 10.2210/pdb2ms4/pdb
• NMR情報: BMRB: 25104
• 分子名称: Peptidyl-prolyl cis-trans isomerase A, Peptide (2 entities in total)
• 機能のキーワード: cyclophilin a, isomerase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P62937
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18991.52

構造登録者

Jankowski, W.,Saleh, T.,Rossi, P.,Kalodimos, C. (登録日: 2014-07-22, 公開日: 2015-09-09, 最終更新日: 2024-05-01)

主引用文献

Saleh, T.,Jankowski, W.,Sriram, G.,Rossi, P.,Shah, S.,Lee, K.B.,Cruz, L.A.,Rodriguez, A.J.,Birge, R.B.,Kalodimos, C.G.
Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway.
Nat.Chem.Biol., 12:117-123, 2016

PubMed Abstract: Cyclophilin A (CypA) is overexpressed in a number of human cancer types, but the mechanisms by which the protein promotes oncogenic properties of cells are not understood. Here we demonstrate that CypA binds the CrkII adaptor protein and prevents it from switching to the inhibited state. CrkII influences cell motility and invasion by mediating signaling through its SH2 and SH3 domains. CrkII Tyr221 phosphorylation by the Abl or EGFR kinases induces an inhibited state of CrkII by means of an intramolecular SH2-pTyr221 interaction, causing signaling interruption. We show that the CrkII phosphorylation site constitutes a binding site for CypA. Recruitment of CypA sterically restricts the accessibility of Tyr221 to kinases, thereby suppressing CrkII phosphorylation and promoting the active state. Structural, biophysical and in vivo data show that CypA augments CrkII-mediated signaling. A strong stimulation of cell migration is observed in cancer cells wherein both CypA and CrkII are greatly upregulated.

PubMed: 26656091
DOI: 10.1038/nchembio.1981

実験手法

SOLUTION NMR