 |
PDBsum entry 1qav
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Membrane protein/oxidoreductase
|
PDB id
|
|
|
|
1qav
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Unexpected modes of pdz domain scaffolding revealed by structure of nnos-Syntrophin complex.
|
|
|
Authors
|
|
B.J.Hillier,
K.S.Christopherson,
K.E.Prehoda,
D.S.Bredt,
W.A.Lim.
|
|
|
Ref.
|
|
Science, 1999,
284,
812-815.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The PDZ protein interaction domain of neuronal nitric oxide synthase (nNOS) can
heterodimerize with the PDZ domains of postsynaptic density protein 95 and
syntrophin through interactions that are not mediated by recognition of a
typical carboxyl-terminal motif. The nNOS-syntrophin PDZ complex structure
revealed that the domains interact in an unusual linear head-to-tail
arrangement. The nNOS PDZ domain has two opposite interaction surfaces-one face
has the canonical peptide binding groove, whereas the other has a beta-hairpin
"finger." This nNOS beta finger docks in the syntrophin peptide
binding groove, mimicking a peptide ligand, except that a sharp beta turn
replaces the normally required carboxyl terminus. This structure explains how
PDZ domains can participate in diverse interaction modes to assemble protein
networks.
|
|
|
|
|
|
|
|
Figure 1.
Fig. 1. Linear head-to-tail heterodimer of nNOS-syntrophin PDZ
domains. (A) The nNOS PDZ domain (orange) has a polarized
structure with distinct receptor (peptide binding groove) and
ligand (  -finger)
faces. The nNOS ligand face docks against the syntrophin PDZ
domain (purple) peptide binding groove. (B) Structure of the
syntrophin PDZ domain (purple) in complex with a COOH-terminal
peptide (orange) (10). The figure was generated with the program
MOLSCRIPT (25).
|
|
Figure 3.
Fig. 3. Recognition of internal motifs by PDZ domains. In (A)
through (C), the GLGF loop acts as a steric block at the end of
the binding groove, necessitating chain termination or a sharp
turn
immediately after the recognition motif. (A) Interaction
topology of a COOH-terminal peptide (orange) bound to PSD-95
PDZ3 (purple surface). (B) Interaction topology of the nNOS finger
(orange) with the syntrophin PDZ domain (purple surface). In (A)
and (B), the hydrophobic ligand residue that packs at site 0 is
shown in space-filling mode. Gray, carbon; red, oxygen. (C)
Schematic of structural requirements for PDZ domain recognition
of internal or COOH-terminal ligands. (D) Rigidly stabilized
structure of nNOS finger.
Overlay of C  traces of
the uncomplexed (orange) and complexed (grey) nNOS PDZ domain
structures, highlighting residues that stabilize the nNOS -finger
conformation. The main interaction is a salt bridge between
Arg^121 and Asp^62, which is buried by the surrounding
hydrophobic residues Ile^16, Leu^57, Pro^100, Phe^103, Thr^105,
Leu^107, and Thr^123. (E) Increased contact area in the PDZ
heterodimer through tertiary interactions. Solvent excluded
footprint of the nNOS PDZ domain (C trace
shown in orange) bound to the syntrophin PDZ domain (purple
surface, ~800 Å^2), compared to the footprint of a peptide
ligand (pink surface, ~400 Å^2). Images were generated
with the programs MOLSCRIPT (25) and WebLab Viewer Lite (26).
|
|
|
|
|
|
The above figures are
reprinted
by permission from the AAAs:
Science
(1999,
284,
812-815)
copyright 1999.
|
|
|
|
|
|
|
