4UX9

Crystal structure of JNK1 bound to a MKK7 docking motif

Summary for 4UX9

• Entry DOI: 10.2210/pdb4ux9/pdb
• Descriptor: MITOGEN-ACTIVATED PROTEIN KINASE 8, DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 7, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: transferase, jnk1, intrinsically disordered domains, mkk7
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 8
• Total formula weight: 177515.40

Authors

Kragelj, J.,Palencia, A.,Nanao, M.H.,Maurin, D.,Bouvignies, G.,Blackledge, M.,Ringkjobing-Jensen, M. (deposition date: 2014-08-20, release date: 2015-03-25, Last modification date: 2024-01-10)

Primary citation

Kragelj, J.,Palencia, A.,Nanao, M.H.,Maurin, D.,Bouvignies, G.,Blackledge, M.,Jensen, M.R.
Structure and Dynamics of the Mkk7-Jnk Signaling Complex.
Proc.Natl.Acad.Sci.USA, 112:3409-, 2015

PubMed Abstract: Signaling specificity in the mitogen-activated protein kinase (MAPK) pathways is controlled by disordered domains of the MAPK kinases (MKKs) that specifically bind to their cognate MAPKs via linear docking motifs. MKK7 activates the c-Jun N-terminal kinase (JNK) pathway and is the only MKK containing three motifs within its regulatory domain. Here, we characterize the conformational behavior and interaction mechanism of the MKK7 regulatory domain. Using NMR spectroscopy, we develop an atomic resolution ensemble description of MKK7, revealing highly diverse intrinsic conformational propensities of the three docking sites, suggesting that prerecognition sampling of the bound-state conformation is not prerequisite for binding. Although the different sites exhibit similar affinities for JNK1, interaction kinetics differ considerably. Importantly, we determine the crystal structure of JNK1 in complex with the second docking site of MKK7, revealing two different binding modes of the docking motif correlating with observations from NMR exchange spectroscopy. Our results provide unique insight into how signaling specificity is regulated by linear motifs and, in general, into the role of conformational disorder in MAPK signaling.

PubMed: 25737554
DOI: 10.1073/PNAS.1419528112

Experimental method

X-RAY DIFFRACTION (2.34 Å)