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PDBsum entry 1dp4
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Hormone/growth factor receptor, lyase
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PDB id
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1dp4
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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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Structure of the dimerized hormone-Binding domain of a guanylyl-Cyclase-Coupled receptor.
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Authors
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F.Van den akker,
X.Zhang,
M.Miyagi,
X.Huo,
K.S.Misono,
V.C.Yee.
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Ref.
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Nature, 2000,
406,
101-104.
[DOI no: ]
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PubMed id
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Abstract
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The atrial natriuretic peptide (ANP) hormone is secreted by the heart in
response to an increase in blood pressure. ANP exhibits several potent
anti-hypertensive actions in the kidney, adrenal gland and vascular system.
These actions are induced by hormone binding extracellularly to the ANP
receptor, thereby activating its intracellular guanylyl cyclase domain for the
production of cyclic GMP. Here we present the crystal structure of the
glycosylated dimerized hormone-binding domain of the ANP receptor at 2.0-A
resolution. The monomer comprises two interconnected subdomains, each
encompassing a central beta-sheet flanked by alpha-helices, and exhibits the
type I periplasmic binding protein fold. Dimerization is mediated by the
juxtaposition of four parallel helices, arranged two by two, which brings the
two protruding carboxy termini into close relative proximity. From affinity
labelling and mutagenesis studies, the ANP-binding site maps to the side of the
dimer crevice and extends to near the dimer interface. A conserved
chloride-binding site is located in the membrane distal domain, and we found
that hormone binding is chloride dependent. These studies suggest mechanisms for
hormone activation and the allostery of the ANP receptor.
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Figure 1.
Figure 1: Crystal structure of the ANP receptor hormone-binding
domain dimer. a, Ribbon diagram showing disulphide bonds
(red), glycosylation (purple ball-and-stick), disordered
glycosylation sites (purple spheres) and bound chlorides
(yellow). The extrapolated C terminus of the second monomer
(blue) and two transmembrane helices are modelled. b, The
ANP-binding site on the receptor, shown as a space-filling
model. M173 and H195 (blue), E169 and H185 (red), H185 and A202
(green), and Y88 and Y120 are highlighted. Residues 98, 113,
115, 158, 166 and the common E169 (light brown, 115 is hidden
from view) are structurally equivalent to AmiC residues that
interact with AmiR6. The dark grey 262-269 loop reaches over
from the second monomer and forms a concave surface at one edge
of the binding site that may be involved in hormone
interactions. c, As b, but rotated 85° about the horizontal
axis. d, Electrostatic surface representation generated using
GRASP29, with positive and negative charges in blue and red,
respectively, and the putative effector pocket labelled 'E'.
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Figure 2.
Figure 2: The chloride-binding site in the ligand-binding domain
of the ANP receptor. A 25-4-Å resolution anomalous difference
Fourier electron density contoured at 5  is
shown in blue.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2000,
406,
101-104)
copyright 2000.
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