PDBsum entry 2qkd

Signaling protein, cell cycle

PDB id: 2qkd

Contents

Protein chain

384 a.a. *

Ligands

FMT

Metals

_ZN ×2

Waters ×275

* Residue conservation analysis

PDB id:

2qkd

Name:

Signaling protein, cell cycle

Title:

Crystal structure of tandem zpr1 domains

Structure:

Zinc finger protein zpr1. Chain: a. Synonym: zinc finger protein 259. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: znf259, zfp259, zpr1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.00Å R-factor: 0.208 R-free: 0.247

Authors:

A.K.Mishra

Key ref:

A.K.Mishra et al. (2007). Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes. Proc Natl Acad Sci U S A, 104, 13930-13935. PubMed id: 17704259 DOI: 10.1073/pnas.0704915104

Date:

10-Jul-07 Release date: 07-Aug-07

Protein chain

Q62384  (ZPR1_MOUSE) -  Zinc finger protein ZPR1 from Mus musculus

Seq: 459 a.a.

Struc: 384 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.0704915104

Proc Natl Acad Sci U S A 104:13930-13935 (2007)

PubMed id: 17704259

Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes.

A.K.Mishra, L.Gangwani, R.J.Davis, D.G.Lambright.

ABSTRACT

Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded beta helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1Balpha from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. Structure-based mutational and complementation analyses reveal a conserved binding epitope for eEF1A that is required for normal cell growth, proliferation, and cell cycle progression. Structural differences between the ZPR1 domains contribute to the observed functional divergence and provide evidence for distinct modalities of interaction with eEF1A and survival motor neuron complexes.

Selected figure(s)

Figure 1.
Domain organization and tertiary structure of ZPR1. (A) Schematic illustration of the modular architecture of ZPR1, which consists of two homologous Zn^2+ finger-A/B domain modules. (B) Ribbon representation of the tertiary structure of ZPR1. (C) Structural alignment of the first ZnF in ZPR1 with the ZnF in eEIF2. (D) Structural alignment of the β-helix in the ZPR1 A domain with the β-helix in the Trp RNA-binding protein TRAP.

Figure 2.
Identification of putative conserved interaction epitopes in ZPR1 for receptors and SMN complexes. (A) Conservation of residues between ZnF1 and ZnF2 mapped to the surface of ZPR1. (B) Conservation of exposed residues in the ZnF2-B domain modules of ZPR1 homologues. (C) Conservation of residues buried in the interface between ZnF2 and the B domain of ZPR1 homologues.

Figures were selected by an automated process.