PDBsum entry 2m6y

Chaperone

PDB id: 2m6y

Contents

Protein chain

77 a.a.

PDB id:

2m6y

Name:

Chaperone

Title:

The solution structure of the j-domain of human dnaja1

Structure:

Dnaj homolog subfamily a member 1. Chain: a. Fragment: j-domain (unp residues 1-67). Synonym: dnaj protein homolog 2, hsdj, heat shock 40 kda protein 4, heat shock protein j2, hsj-2, human dnaj protein 2, hdj-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dnaja1, dnaj2, hdj2, hsj2, hspf4. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

J.L.Stark,K.Mehla,N.Chaika,T.B.Acton,R.Xiao,P.K.Singh,G.T.Montelione, R.Powers,Northeast Structural Genomics Consortium (Nesg)

Key ref:

J.L.Stark et al. (2014). Structure and function of human DnaJ homologue subfamily a member 1 (DNAJA1) and its relationship to pancreatic cancer. Biochemistry, 53, 1360-1372. PubMed id: 24512202 DOI: 10.1021/bi401329a

Date:

14-Apr-13 Release date: 26-Jun-13

Protein chain

P31689  (DNJA1_HUMAN) -  DnaJ homolog subfamily A member 1 from Homo sapiens

Seq: 397 a.a.

Struc: 77 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/bi401329a

Biochemistry 53:1360-1372 (2014)

PubMed id: 24512202

Structure and function of human DnaJ homologue subfamily a member 1 (DNAJA1) and its relationship to pancreatic cancer.

J.L.Stark, K.Mehla, N.Chaika, T.B.Acton, R.Xiao, P.K.Singh, G.T.Montelione, R.Powers.

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.