8RPP

Crystal structure of the JIP1-JIP2-SH3 heterodimer and the JIP2-JIP2-SH3 homodimer

8RPP の概要

• エントリーDOI: 10.2210/pdb8rpp/pdb
• 関連するPDBエントリー: 7NYK
• 分子名称: C-Jun-amino-terminal kinase-interacting protein 2, C-Jun-amino-terminal kinase-interacting protein 1 (3 entities in total)
• 機能のキーワード: regulation of jnk cascade, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 29535.69

構造登録者

Palencia, A.,Marino-Perez, L.,Ielasi, F.I.,Jensen, M.R. (登録日: 2024-01-16, 公開日: 2024-07-10, 最終更新日: 2024-09-18)

主引用文献

Marino Perez, L.,Ielasi, F.S.,Lee, A.,Delaforge, E.,Juyoux, P.,Tengo, M.,Davis, R.J.,Palencia, A.,Jensen, M.R.
Structural basis of homodimerization of the JNK scaffold protein JIP2 and its heterodimerization with JIP1.
Structure, 32:1394-, 2024

PubMed Abstract: The scaffold proteins JIP1 and JIP2 intervene in the c-Jun N-terminal kinase (JNK) pathway to mediate signaling specificity by coordinating the simultaneous assembly of multiple kinases. Using NMR, we demonstrate that JIP1 and JIP2 heterodimerize via their SH3 domains with the affinity of heterodimerization being comparable to homodimerization. We present the high-resolution crystal structure of the JIP2-SH3 homodimer and the JIP1-JIP2-SH3 heterodimeric complex. The JIP2-SH3 structure reveals how charge differences in residues at its dimer interface lead to formation of compensatory hydrogen bonds and salt bridges, distinguishing it from JIP1-SH3. In the JIP1-JIP2-SH3 complex, structural features of each homodimer are employed to stabilize the heterodimer. Building on these insights, we identify key residues crucial for stabilizing the dimer of both JIP1 and JIP2. Through targeted mutations in cellulo, we demonstrate a functional role for the dimerization of the JIP1 and JIP2 scaffold proteins in activation of the JNK signaling pathway.

PubMed: 39013462
DOI: 10.1016/j.str.2024.06.010

実験手法

X-RAY DIFFRACTION (1.867 Å)