PDBsum entry 4j0b

Chaperone

PDB id: 4j0b

Contents

Protein chains

594 a.a.

609 a.a.

Ligands

ADP-BEF ×2

Metals

_MG ×2

_CO ×4

Waters ×187

PDB id:

4j0b

Name:

Chaperone

Title:

Structure of mitochondrial hsp90 (trap1) with adp-bef3

Structure:

Tnf receptor-associated protein 1. Chain: a, b. Fragment: unp residues 73-719. Synonym: trap1 protein. Engineered: yes

Source:

Danio rerio. Leopard danio,zebra danio,zebra fish. Organism_taxid: 7955. Gene: trap1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.35Å R-factor: 0.207 R-free: 0.248

Authors:

J.R.Partridge,L.A.Lavery,D.A.Agard

Key ref:

L.A.Lavery et al. (2014). Structural asymmetry in the closed state of mitochondrial Hsp90 (TRAP1) supports a two-step ATP hydrolysis mechanism. Mol Cell, 53, 330-343. PubMed id: 24462206 DOI: 10.1016/j.molcel.2013.12.023

Date:

30-Jan-13 Release date: 22-Jan-14

Protein chain

A8WFV1  (A8WFV1_DANRE) -  Heat shock protein 75 kDa, mitochondrial from Danio rerio

Seq: 719 a.a.

Struc: 594 a.a.

Protein chain

A8WFV1  (A8WFV1_DANRE) -  Heat shock protein 75 kDa, mitochondrial from Danio rerio

Seq: 719 a.a.

Struc: 609 a.a.

DOI no: 10.1016/j.molcel.2013.12.023

Mol Cell 53:330-343 (2014)

PubMed id: 24462206

Structural asymmetry in the closed state of mitochondrial Hsp90 (TRAP1) supports a two-step ATP hydrolysis mechanism.

L.A.Lavery, J.R.Partridge, T.A.Ramelot, D.Elnatan, M.A.Kennedy, D.A.Agard.

ABSTRACT

While structural symmetry is a prevailing feature of homo-oligomeric proteins, asymmetry provides unique mechanistic opportunities. We present the crystal structure of full-length TRAP1, the mitochondrial Hsp90 molecular chaperone, in a catalytically active closed state. The TRAP1 homodimer adopts a distinct, asymmetric conformation, where one protomer is reconfigured via a helix swap at the middle:C-terminal domain (MD:CTD) interface. This interface plays a critical role in client binding. Solution methods validate the asymmetry and show extension to Hsp90 homologs. Point mutations that disrupt unique contacts at each MD:CTD interface reduce catalytic activity and substrate binding and demonstrate that each protomer needs access to both conformations. Crystallographic data on a dimeric NTD:MD fragment suggests that asymmetry arises from strain induced by simultaneous NTD and CTD dimerization. The observed asymmetry provides the potential for an additional step in the ATPase cycle, allowing sequential ATP hydrolysis steps to drive both client remodeling and client release.