2M6Y
The solution structure of the J-domain of human DnaJA1
Summary for 2M6Y
| Entry DOI | 10.2210/pdb2m6y/pdb |
| NMR Information | BMRB: 19163 |
| Descriptor | DnaJ homolog subfamily A member 1 (1 entity in total) |
| Functional Keywords | protein, chaperone, structural genomics, psi-biology, northeast structural genomics consortium, nesg |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane ; Lipid-anchor : P31689 |
| Total number of polymer chains | 1 |
| Total formula weight | 9095.30 |
| Authors | Stark, J.L.,Mehla, K.,Chaika, N.,Acton, T.B.,Xiao, R.,Singh, P.K.,Montelione, G.T.,Powers, R.,Northeast Structural Genomics Consortium (NESG) (deposition date: 2013-04-14, release date: 2013-06-26, Last modification date: 2024-05-01) |
| Primary citation | Stark, J.L.,Mehla, K.,Chaika, N.,Acton, T.B.,Xiao, R.,Singh, P.K.,Montelione, G.T.,Powers, R. Structure and function of human DnaJ homologue subfamily a member 1 (DNAJA1) and its relationship to pancreatic cancer. Biochemistry, 53:1360-1372, 2014 Cited by PubMed Abstract: Pancreatic cancer has a dismal 5 year survival rate of 5.5% that has not been improved over the past 25 years despite an enormous amount of effort. Thus, there is an urgent need to identify truly novel yet druggable protein targets for drug discovery. The human protein DnaJ homologue subfamily A member 1 (DNAJA1) was previously shown to be downregulated 5-fold in pancreatic cancer cells and has been targeted as a biomarker for pancreatic cancer, but little is known about the specific biological function for DNAJA1 or the other members of the DnaJ family encoded in the human genome. Our results suggest the overexpression of DNAJA1 suppresses the stress response capabilities of the oncogenic transcription factor, c-Jun, and results in the diminution of cell survival. DNAJA1 likely activates a DnaK protein by forming a complex that suppresses the JNK pathway, the hyperphosphorylation of c-Jun, and the anti-apoptosis state found in pancreatic cancer cells. A high-quality nuclear magnetic resonance solution structure of the J-domain of DNAJA1 combined with a bioinformatics analysis and a ligand affinity screen identifies a potential DnaK binding site, which is also predicted to overlap with an inhibitory binding site, suggesting DNAJA1 activity is highly regulated. PubMed: 24512202DOI: 10.1021/bi401329a PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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