2MS4

Cyclophilin a complexed with a fragment of crk-ii

Summary for 2MS4

• Entry DOI: 10.2210/pdb2ms4/pdb
• NMR Information: BMRB: 25104
• Descriptor: Peptidyl-prolyl cis-trans isomerase A, Peptide (2 entities in total)
• Functional Keywords: cyclophilin a, isomerase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P62937
• Total number of polymer chains: 2
• Total formula weight: 18991.52

Authors

Jankowski, W.,Saleh, T.,Rossi, P.,Kalodimos, C. (deposition date: 2014-07-22, release date: 2015-09-09, Last modification date: 2024-05-01)

Primary citation

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

Experimental method

SOLUTION NMR