6JPV
Structural analysis of AIMP2-DX2 and HSP70 interaction
Summary for 6JPV
| Entry DOI | 10.2210/pdb6jpv/pdb |
| Descriptor | Heat shock 70 kDa protein 1A,Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (2 entities in total) |
| Functional Keywords | hsp70, aimp2-dx2, substrate binding domain, chaperone |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 33738.04 |
| Authors | Cho, H.Y.,Son, S.Y.,Jeon, Y.H. (deposition date: 2019-03-28, release date: 2019-10-02, Last modification date: 2023-11-22) |
| Primary citation | Lim, S.,Cho, H.Y.,Kim, D.G.,Roh, Y.,Son, S.Y.,Mushtaq, A.U.,Kim, M.,Bhattarai, D.,Sivaraman, A.,Lee, Y.,Lee, J.,Yang, W.S.,Kim, H.K.,Kim, M.H.,Lee, K.,Jeon, Y.H.,Kim, S. Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development. Nat.Chem.Biol., 16:31-41, 2020 Cited by PubMed Abstract: A tumorigenic factor, AIMP2 lacking exon 2 (AIMP2-DX2), is often upregulated in many cancers. However, how its cellular level is determined is not understood. Here, we report heat-shock protein HSP70 as a critical determinant for the level of AIMP2-DX2. Interaction of the two factors was identified by interactome analysis and structurally determined by X-ray crystallography and NMR analyses. HSP70 recognizes the amino (N)-terminal flexible region, as well as the glutathione S-transferase domain of AIMP2-DX2, via its substrate-binding domain, thus blocking the Siah1-dependent ubiquitination of AIMP2-DX2. AIMP2-DX2-induced cell transformation and cancer progression in vivo was further augmented by HSP70. A positive correlation between HSP70 and AIMP2-DX2 levels was shown in various lung cancer cell lines and patient tissues. Chemical intervention in the AIMP2-DX2-HSP70 interaction suppressed cancer cell growth in vitro and in vivo. Thus, this work demonstrates the importance of the interaction between AIMP2-DX2 and HSP70 on tumor progression and its therapeutic potential against cancer. PubMed: 31792442DOI: 10.1038/s41589-019-0415-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.15000649024 Å) |
Structure validation
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