5ETF

Structure of dead kinase MAPK14 with bound the KIM domain of MKK6

Summary for 5ETF

• Entry DOI: 10.2210/pdb5etf/pdb
• Descriptor: Mitogen-activated protein kinase 14, Dual specificity mitogen-activated protein kinase kinase 6 (3 entities in total)
• Functional Keywords: mapk14, mkk6, kim domain, peptide-protein complex, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : Q16539; Nucleus : P52564
• Total number of polymer chains: 2
• Total formula weight: 42999.23

Authors

Pellegrini, E.,Palencia, A.,Braun, L.,Kapp, U.,Bougdour, A.,Belrhali, H.,Bowler, M.W.,Hakimi, M. (deposition date: 2015-11-17, release date: 2016-10-26, Last modification date: 2024-05-08)

Primary citation

Pellegrini, E.,Palencia, A.,Braun, L.,Kapp, U.,Bougdour, A.,Belrhali, H.,Bowler, M.W.,Hakimi, M.A.
Structural Basis for the Subversion of MAP Kinase Signaling by an Intrinsically Disordered Parasite Secreted Agonist.
Structure, 25:16-26, 2017

PubMed Abstract: The causative agent of toxoplasmosis, the intracellular parasite Toxoplasma gondii, delivers a protein, GRA24, into the cells it infects that interacts with the mitogen-activated protein (MAP) kinase p38α (MAPK14), leading to activation and nuclear translocation of the host kinase and a subsequent inflammatory response that controls the progress of the parasite. The purification of a recombinant complex of GRA24 and human p38α has allowed the molecular basis of this activation to be determined. GRA24 is shown to be intrinsically disordered, binding two kinases that act independently, and is the only factor required to bypass the canonical mitogen-activated protein kinase activation pathway. An adapted kinase interaction motif (KIM) forms a highly stable complex that competes with cytoplasmic regulatory partners. In addition, the recombinant complex forms a powerful in vitro tool to evaluate the specificity and effectiveness of p38α inhibitors that have advanced to clinical trials, as it provides a hitherto unavailable stable and highly active form of p38α.

PubMed: 27889209
DOI: 10.1016/j.str.2016.10.011

Experimental method

X-RAY DIFFRACTION (2.4 Å)