3A8Y

Crystal structure of the complex between the BAG5 BD5 and Hsp70 NBD

Summary for 3A8Y

• Entry DOI: 10.2210/pdb3a8y/pdb
• Descriptor: Heat shock 70 kDa protein 1, BAG family molecular chaperone regulator 5, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: bag domain, hsp70, atpase domain, protein complex, triple helix, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P08107
• Total number of polymer chains: 4
• Total formula weight: 118886.37

Authors

Arakawa, A.,Handa, N.,Ohsawa, N.,Shirouzu, M.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2009-10-13, release date: 2010-03-31, Last modification date: 2024-10-16)

Primary citation

Arakawa, A.,Handa, N.,Ohsawa, N.,Shida, M.,Kigawa, T.,Hayashi, F.,Shirouzu, M.,Yokoyama, S.
The C-terminal BAG domain of BAG5 induces conformational changes of the Hsp70 nucleotide-binding domain for ADP-ATP exchange
Structure, 18:309-319, 2010

PubMed Abstract: ADP-ATP exchange by the molecular chaperone Hsp70 is enhanced by several cochaperones. BAG5 consists of five BAG domains and associates with the nucleotide-binding domain (NBD) of Hsp70. The overexpression of BAG5 in the cytosol reportedly disturbs Hsp70-mediated protein refolding and induces Parkinson's disease. In the present study, we found that the fifth BAG domain (BD5) of BAG5 is responsible for the interaction between Hsp70 and BAG5. We also determined the crystal structures of the BD5*NBD complex. BD5 binding caused two different types of NBD conformational changes, which both disrupted the nucleotide-binding groove. In fact, BD5 reduced the affinity of the NBD for ADP. Moreover, BD5, as well as the full-length BAG5, accelerated Hsp70-mediated refolding in an in vitro assay. Therefore, BAG5 can function as the nucleotide exchange factor of Hsp70 for the enhancement of protein refolding.

PubMed: 20223214
DOI: 10.1016/j.str.2010.01.004

Experimental method

X-RAY DIFFRACTION (2.3 Å)