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PDBsum entry 1fe0
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Metal transport
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PDB id
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1fe0
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Contents |
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* Residue conservation analysis
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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 basis for copper transfer by the metallochaperone for the menkes/wilson disease proteins.
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Authors
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A.K.Wernimont,
D.L.Huffman,
A.L.Lamb,
T.V.O'Halloran,
A.C.Rosenzweig.
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Ref.
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Nat Struct Biol, 2000,
7,
766-771.
[DOI no: ]
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PubMed id
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Abstract
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The Hah1 metallochaperone protein is implicated in copper delivery to the Menkes
and Wilson disease proteins. Hah1 and the N-termini of its target proteins
belong to a family of metal binding domains characterized by a conserved
MT/HCXXC sequence motif. The crystal structure of Hah1 has been determined in
the presence of Cu(I), Hg(II), and Cd(II). The 1.8 A resolution structure of
CuHah1 reveals a copper ion coordinated by Cys residues from two adjacent Hah1
molecules. The CuHah1 crystal structure is the first of a copper chaperone bound
to copper and provides structural support for direct metal ion exchange between
conserved MT/HCXXC motifs in two domains. The structures of HgHah1 and CdHah1,
determined to 1.75 A resolution, also reveal metal ion coordination by two
MT/HCXXC motifs. An extended hydrogen bonding network, unique to the complex of
two Hah1 molecules, stabilizes the metal binding sites and suggests specific
roles for several conserved residues. Taken together, the structures provide
models for intermediates in metal ion transfer and suggest a detailed molecular
mechanism for protein recognition and metal ion exchange between MT/HCXXC
containing domains.
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Figure 1.
Figure 1. Structure of CuHah1. Monomer A is shown in blue and
monomer B is shown in yellow. The copper ion is shown as a cyan
sphere, and the four Cys residues in the two MT/HCXXC motifs are
shown as ball-and-stick representations. a, Stereo view with the
noncrystallographic two-fold axis running vertically. b, Viewed
90° from the orientation in (a), looking down the molecular
twofold axis.
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Figure 3.
Figure 3. Hydrogen bonding interactions. a, Stereo view of
the extended hydrogen bonding network at the metal binding site
in CuHah1. Monomer A is shown in blue, monomer B is shown in
yellow, and the copper ion is shown as a cyan sphere. b, Surface
representation of Hah1 color coded according to electrostatic
potential: red, -20 kT; white 0 kT; blue, +20 kT. The upper
right inset shows the orientation of the two Hah1 molecules. c,
Surface representation of a model of Hah1 docked with the
Menkes4 domain (PDB accession code 2AW0), color coded as in (b).
The Menkes4 domain was superimposed on monomer A of Hah1 to
generate the model. In the upper right inset, the Menkes4 domain
is shown in magenta and monomer B of Hah1 is shown in yellow.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2000,
7,
766-771)
copyright 2000.
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