PDBsum entry 4j8f

Chaperone

PDB id: 4j8f

Contents

Protein chain

551 a.a.

Ligands

ADP

PO4

Metals

IOD ×17

_MG

Waters ×45

PDB id:

4j8f

Name:

Chaperone

Title:

Crystal structure of a fusion protein containing the nbd of hsp70 and the middle domain of hip

Structure:

Heat shock 70 kda protein 1a/1b, hsc70-interacting protein. Chain: a. Fragment: p08107 residues 1-382, p50503 residues 77-247. Engineered: yes. Other_details: hsp70(1-382)-hip(77-247) fusion protein

Source:

Homo sapiens, rattus norvegicus. Human, brown rat,rat,rats. Organism_taxid: 9606, 10116. Gene: hspa1, hspa1a, hspa1b, st13, fam10a1, hip, hspa1a, st13. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.70Å R-factor: 0.197 R-free: 0.261

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 chain

P0DMV8  (HS71A_HUMAN) -  Heat shock 70 kDa protein 1A from Homo sapiens

Seq: 641 a.a.

Struc: 551 a.a.*

Protein chain

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

Seq: 368 a.a.

Struc: 551 a.a.*

* PDB and UniProt seqs differ at 229 residue positions (black crosses)

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.