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PDBsum entry 2qkd
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Signaling protein, cell cycle
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PDB id
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2qkd
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References listed in PDB file
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Key reference
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Title
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Structural insights into the interaction of the evolutionarily conserved zpr1 domain tandem with eukaryotic ef1a, Receptors, And smn complexes.
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Authors
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A.K.Mishra,
L.Gangwani,
R.J.Davis,
D.G.Lambright.
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Ref.
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Proc Natl Acad Sci U S A, 2007,
104,
13930-13935.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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