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PDBsum entry 1g9o
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Signaling protein
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PDB id
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1g9o
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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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Crystal structure of the pdz1 domain of human na(+)/h(+) exchanger regulatory factor provides insights into the mechanism of carboxyl-Terminal leucine recognition by class i pdz domains.
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Authors
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S.Karthikeyan,
T.Leung,
G.Birrane,
G.Webster,
J.A.Ladias.
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Ref.
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J Mol Biol, 2001,
308,
963-973.
[DOI no: ]
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PubMed id
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Abstract
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The Na(+)/H(+) exchanger regulatory factor (NHERF; also known as EBP50) contains
two PDZ domains that mediate the assembly of transmembrane and cytosolic
proteins into functional signal transduction complexes. The NHERF PDZ1 domain
interacts specifically with the motifs DSLL, DSFL, and DTRL present at the
carboxyl termini of the beta(2) adrenergic receptor (beta(2)AR), the
platelet-derived growth factor receptor (PDGFR), and the cystic fibrosis
transmembrane conductance regulator (CFTR), respectively, and plays a central
role in the physiological regulation of these proteins. The crystal structure of
the human NHERF PDZ1 has been determined at 1.5 A resolution using
multiwavelength anomalous diffraction phasing. The overall structure is similar
to known PDZ structures, with notable differences in the NHERF PDZ1
carboxylate-binding loop that contains the GYGF motif, and the variable loop
between the beta2 and beta3 strands. In the crystalline state, the
carboxyl-terminal sequence DEQL of PDZ1 occupies the peptide-binding pocket of a
neighboring PDZ1 molecule related by 2-fold crystallographic symmetry. This
structure reveals the molecular mechanism of carboxyl-terminal leucine
recognition by class I PDZ domains, and provides insights into the specificity
of NHERF interaction with the carboxyl termini of several membrane receptors and
ion channels, including the beta(2)AR, PDGFR, and CFTR.
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Figure 7.
Figure 7. Two-dimensional schematic representation of the
contacts observed in the NHERF PDZ1 binding pocket. PDZ1
residues (orange) making hydrogen bonds and hydrophobic contacts
with the peptide ligand (purple) are shown in ball-and-stick
representation. Carbon atoms are shown in white, oxygen atoms in
red, and nitrogen atoms in blue. Water molecules are shown as
green spheres. Hydrogen bonds are depicted as broken lines and
numbers indicate distances in Å. Val76 involved in
hydrophobic interaction with the C^d2 atom of Leu0 is shown as
an arc with radial spokes. The Figure was generated using the
program LIGPLOT[49].
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Figure 8.
Figure 8. Carboxyl-terminal leucine and valine recognition
by PDZ domains. Surface representation of the hydrophobic
pockets of (a) human NHERF PDZ1 and (b) rat PSD-95 PDZ3 bound to
carboxyl-terminal leucine and valine residues, respectively. The
limits of the hydrophobic cavities are denoted with jagged
edges. The Figure was made with the program GRASP[50].
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2001,
308,
963-973)
copyright 2001.
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Secondary reference #1
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Title
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Nhe-Rf, A regulatory cofactor for na(+)-H+ exchange, Is a common interactor for merlin and erm (merm) proteins.
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Authors
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A.Murthy,
C.Gonzalez-Agosti,
E.Cordero,
D.Pinney,
C.Candia,
F.Solomon,
J.Gusella,
V.Ramesh.
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Ref.
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J Biol Chem, 1998,
273,
1273-1276.
[DOI no: ]
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PubMed id
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Figure 1.
Fig. 1. A, schematic representation of hNHE-RF. Lines
represent the 5  - and 3
-untranslated
region. The coding region is indicated^ by the box. Shaded areas
represent the two PDZ domains. The black area (aa 290-358)
represents the MERM binding domain. B, sequence^ comparison of
human NHE-RF with rabbit and mouse NHE-RF and E3KARP. The amino
acid identities between these sequences are boxed. The^ hNHE-RF
sequence has been deposited in GenBankTM, and the accession
number is A5036241.
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Figure 4.
Fig. 4. A model connecting the Na^+-H+ exchangers of the
plasma membrane to the actin cytoskeleton via the interaction of
hNHE-RF^ to the NF2 tumor suppressor merlin and related ERM
(MERM) proteins.
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The above figures are
reproduced from the cited reference
with permission from the ASBMB
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Secondary reference #2
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Title
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Crystal structure of the hcask pdz domain reveals the structural basis of class ii pdz domain target recognition.
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Authors
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D.L.Daniels,
A.R.Cohen,
J.M.Anderson,
A.T.Brünger.
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Ref.
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Nat Struct Biol, 1998,
5,
317-325.
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PubMed id
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Secondary reference #3
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Title
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Crystal structures of a complexed and peptide-Free membrane protein-Binding domain: molecular basis of peptide recognition by pdz.
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Authors
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D.A.Doyle,
A.Lee,
J.Lewis,
E.Kim,
M.Sheng,
R.Mackinnon.
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Ref.
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Cell, 1996,
85,
1067-1076.
[DOI no: ]
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PubMed id
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Figure 4.
Figure 4. Chemical Interactions Involved in Peptide
Binding(A) Stereo view of the peptide-binding site demonstrating
protein–peptide interactions via hydrogen bonds (dashed white
lines) and the location of the Val 0 side chain in the
hydrophobic pocket. Oxygen atoms are shown in red and nitrogen
atoms in blue. The green sphere shows a well-ordered water
molecule linking the carboxylate group to Arg-318. The picture
was drawn with MOLSCRIPT and Raster3D.(B) Schematic view of the
contacts identified in the crystal structure of the complex.
Dashed lines represent hydrogen bonds, and the two closest
atom-to-atom distances between the Val 0 side chain and all
atoms in the hydrophobic pocket of the PDZ domain are drawn as
solid black lines. The Val 0 side chain makes numerous other Van
der Waals contacts within the range of 3.9 to 4.3 Å;
however, for clarity they are not indicated in this diagram. The
fixed orientation of the arginine guanidinium head group via
hydrogen bonds with backbone carbonyl groups is also shown.
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Figure 6.
Figure 6. Schematic Drawing of a PDZ and an IRS-1 PTB
DomainA shared peptide-binding motif is highlighted in red. In
both domains bound peptide, shown in yellow, forms an
antiparallel β sheet with the β strand flanking the
peptide-binding groove. The schematic of the IRS-1 PTB domain is
based on [39].
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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Secondary reference #4
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Title
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Crystal structure of a pdz domain.
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Authors
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J.H.Morais cabral,
C.Petosa,
M.J.Sutcliffe,
S.Raza,
O.Byron,
F.Poy,
S.M.Marfatia,
A.H.Chishti,
R.C.Liddington.
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Ref.
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Nature, 1996,
382,
649-652.
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PubMed id
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