4H36

Crystal Structure of JNK3 in Complex with ATF2 Peptide

4H36 の概要

• エントリーDOI: 10.2210/pdb4h36/pdb
• 関連するPDBエントリー: 4H39 4H3B
• 分子名称: Mitogen-activated protein kinase 10, Cyclic AMP-dependent transcription factor ATF-2 (3 entities in total)
• 機能のキーワード: kinase, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm : P53779; Nucleus: P15336
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42216.91

構造登録者

Nwachukwu, J.C.,Laughlin, J.D.,Figuera-Losada, M.,Cherry, L.,Nettles, K.W.,LoGrasso, P.V. (登録日: 2012-09-13, 公開日: 2012-11-21, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3 Å)