4J8F

Crystal structure of a fusion protein containing the NBD of Hsp70 and the middle domain of Hip

Summary for 4J8F

• Entry DOI: 10.2210/pdb4j8f/pdb
• Related: 4J8C 4J8D 4J8E
• Descriptor: Heat shock 70 kDa protein 1A/1B, Hsc70-interacting protein, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: actin-like fold, nucleotide binding domain, tetratricopeptide repeat, solenoid, molecular chaperone complex, cytosol, chaperone
• Biological source: Homo sapiens (human, brown rat,rat,rats); More
• Cellular location: Cytoplasm: P50503
• Total number of polymer chains: 1
• Total formula weight: 65122.33

Authors

Li, Z.,Bracher, A. (deposition date: 2013-02-14, release date: 2013-07-03, Last modification date: 2024-02-28)

Primary citation

Li, Z.,Hartl, F.U.,Bracher, A.
Structure and function of Hip, an attenuator of the Hsp70 chaperone cycle.
Nat.Struct.Mol.Biol., 20:929-935, 2013

PubMed Abstract: The Hsp70-interacting protein, Hip, cooperates with the chaperone Hsp70 in protein folding and prevention of aggregation. Hsp70 interacts with non-native protein substrates in an ATP-dependent reaction cycle regulated by J-domain proteins and nucleotide exchange factors (NEFs). Hip is thought to delay substrate release by slowing ADP dissociation from Hsp70. Here we present crystal structures of the dimerization domain and the tetratricopeptide repeat (TPR) domain of rat Hip. As shown in a cocrystal structure, the TPR core of Hip interacts with the Hsp70 ATPase domain through an extensive interface, to form a bracket that locks ADP in the binding cleft. Hip and NEF binding to Hsp70 are mutually exclusive, and thus Hip attenuates active cycling of Hsp70-substrate complexes. This mechanism explains how Hip enhances aggregation prevention by Hsp70 and facilitates transfer of specific proteins to downstream chaperones or the proteasome.

PubMed: 23812373
DOI: 10.1038/nsmb.2608

Experimental method

X-RAY DIFFRACTION (2.7 Å)