PDBsum entry 4j8e

Chaperone

PDB id: 4j8e

Contents

Protein chains

119 a.a.

Ligands

GOL ×2

Waters ×11

PDB id:

4j8e

Name:

Chaperone

Title:

Middle domain of hsc70-interacting protein, crystal form i

Structure:

Hsc70-interacting protein. Chain: a, b. Fragment: unp residues 78-247. Synonym: hip, protein fam10a1, protein st13 homolog. Engineered: yes

Source:

Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: fam10a1, hip, st13. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.60Å R-factor: 0.187 R-free: 0.248

Authors:

Z.Li,A.Bracher

Key ref:

Z.Li et al. (2013). Structure and function of Hip, an attenuator of the Hsp70 chaperone cycle. Nat Struct Biol, 20, 929-935. PubMed id: 23812373 DOI: 10.1038/nsmb.2608

Date:

14-Feb-13 Release date: 03-Jul-13

Protein chains

P50503  (F10A1_RAT) -  Hsc70-interacting protein from Rattus norvegicus

Seq: 368 a.a.

Struc: 119 a.a.

DOI no: 10.1038/nsmb.2608

Nat Struct Biol 20:929-935 (2013)

PubMed id: 23812373

Structure and function of Hip, an attenuator of the Hsp70 chaperone cycle.

Z.Li, F.U.Hartl, A.Bracher.

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.