Summary
PDB 4H36 deposited: 2012-09-13 modified: 2012-12-26
Title Crystal Structure of JNK3 in Complex with ATF2 Peptide
Authors Cherry, L., Figuera-Losada, M., Laughlin, J.D., Lograsso, P.V., Nettles, K.W., Nwachukwu, J.C.
Method X-RAY DIFFRACTION
Structure factors resolution 3.0 rfactor 0.2163 rfree 0.2685
DPI 1.31 theoretical min: 0.59
Related PDB Entries 4H39 4H3B
Citations

c-Jun N-terminal (JNK) family kinases haveĀ a common peptide-docking site used by upstream activating kinases, substrates, scaffold proteins, and phosphatases, where the ensemble of bound proteins determines signaling output. Although there are many JNK structures, little is known about mechanisms of allosteric regulation between the catalytic and peptide-binding sites, and the activation loop, whose phosphorylation is required for catalytic activity. Here, we compare three structures of unliganded JNK3 bound to different peptides. These were compared as a class to structures that differ in binding of peptide, small molecule ligand, or conformation of the kinase activation loop. Peptide binding induced an inhibitory interlobe conformer that was reversed by alterations in the activation loop. Structure class analysis revealed the subtle structural mechanisms for allosteric signaling between the peptide-binding site and activation loop. Biochemical data from isothermal calorimetry, fluorescence energy transfer, and enzyme inhibition demonstrated affinity differences among the three peptides that were consistent with structural observations.

Structure 2012 Dec; 20(12):2174-2184 doi:10.1016/j.str.2012.09.021

Cross References
Database source Identifier Description
PubMed 23142346 STRUE6
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
4H36/1 4H36 1 dimer 0 2 1 2490