PDBsum entry 3hu2

Transport protein

PDB id: 3hu2

Contents

Protein chains

(+ 0 more) 452 a.a. *

Ligands

AGS ×6

Metals

_MG ×6

Waters ×93

* Residue conservation analysis

PDB id:

3hu2

Name:

Transport protein

Title:

Structure of p97 n-d1 r86a mutant in complex with atpgs

Structure:

Transitional endoplasmic reticulum atpase. Chain: a, b, c, d, e, f. Fragment: residues 1-481. Synonym: ter atpase, 15s mg(2+)-atpase p97 subunit, valosin- containing protein, vcp. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Strain: human. Gene: p97, vcp. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.85Å R-factor: 0.259 R-free: 0.290

Authors:

W.-K.Tang

Key ref:

W.K.Tang et al. (2010). A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants. Embo J, 29, 2217-2229. PubMed id: 20512113

Date:

12-Jun-09 Release date: 16-Jun-10

Protein chains

P55072  (TERA_HUMAN) -  Transitional endoplasmic reticulum ATPase from Homo sapiens

Seq: 806 a.a.

Struc: 452 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.6.4.6 - vesicle-fusing ATPase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP (Bound ligand (Het Group name = AGS) matches with 93.75% similarity) + H2O = ADP + phosphate + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Embo J 29:2217-2229 (2010)

PubMed id: 20512113

A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants.

W.K.Tang, D.Li, C.C.Li, L.Esser, R.Dai, L.Guo, D.Xia.

ABSTRACT

Mutations in p97, a major cytosolic AAA (ATPases associated with a variety of cellular activities) chaperone, cause inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD). IBMPFD mutants have single amino-acid substitutions at the interface between the N-terminal domain (N-domain) and the adjacent AAA domain (D1), resulting in a reduced affinity for ADP. The structures of p97 N-D1 fragments bearing IBMPFD mutations adopt an atypical N-domain conformation in the presence of Mg(2+).ATPgammaS, which is reversible by ADP, showing for the first time the nucleotide-dependent conformational change of the N-domain. The transition from the ADP- to the ATPgammaS-bound state is accompanied by a loop-to-helix conversion in the N-D1 linker and by an apparent re-ordering in the N-terminal region of p97. X-ray scattering experiments suggest that wild-type p97 subunits undergo a similar nucleotide-dependent N-domain conformational change. We propose that IBMPFD mutations alter the timing of the transition between nucleotide states by destabilizing the ADP-bound form and consequently interfere with the interactions between the N-domains and their substrates.