8RPP
Crystal structure of the JIP1-JIP2-SH3 heterodimer and the JIP2-JIP2-SH3 homodimer
Summary for 8RPP
| Entry DOI | 10.2210/pdb8rpp/pdb |
| Related | 7NYK |
| Descriptor | C-Jun-amino-terminal kinase-interacting protein 2, C-Jun-amino-terminal kinase-interacting protein 1 (3 entities in total) |
| Functional Keywords | regulation of jnk cascade, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 29535.69 |
| Authors | Palencia, A.,Marino-Perez, L.,Ielasi, F.I.,Jensen, M.R. (deposition date: 2024-01-16, release date: 2024-07-10, Last modification date: 2024-09-18) |
| Primary citation | 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 Cited by 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: 39013462DOI: 10.1016/j.str.2024.06.010 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.867 Å) |
Structure validation
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