4H39

Crystal Structure of JNK3 in Complex with JIP1 Peptide

Summary for 4H39

• Entry DOI: 10.2210/pdb4h39/pdb
• Related: 4H36 4H3B
• Descriptor: Mitogen-activated protein kinase 10, C-Jun-amino-terminal kinase-interacting protein 1 (3 entities in total)
• Functional Keywords: mapk, kinase, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : P53779 Q9UQF2
• Total number of polymer chains: 2
• Total formula weight: 42369.06

Authors

Nwachukwu, J.C.,Laughlin, J.D.,Figuera-Losada, M.,Cherry, L.,Nettles, K.W.,LoGrasso, P.V. (deposition date: 2012-09-13, release date: 2012-11-21, Last modification date: 2023-09-20)

Primary citation

Laughlin, J.D.,Nwachukwu, J.C.,Figuera-Losada, M.,Cherry, L.,Nettles, K.W.,Lograsso, P.V.
Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases.
Structure, 20:2174-2184, 2012

PubMed Abstract: c-Jun N-terminal (JNK) family kinases have 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.

PubMed: 23142346
DOI: 10.1016/j.str.2012.09.021

Experimental method

X-RAY DIFFRACTION (1.992 Å)