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PDBsum entry 2g2l
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Membrane protein
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PDB id
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2g2l
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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 second pdz domain of sap97 in complex with a glur-A c-Terminal peptide.
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Authors
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I.Von ossowski,
E.Oksanen,
L.Von ossowski,
C.Cai,
M.Sundberg,
A.Goldman,
K.Keinänen.
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Ref.
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Febs J, 2006,
273,
5219-5229.
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PubMed id
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Abstract
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Synaptic targeting of GluR-A subunit-containing glutamate receptors involves an
interaction with synapse-associated protein 97 (SAP97). The C-terminus of
GluR-A, which contains a class I PDZ ligand motif (-x-Ser/Thr-x-phi-COOH where
phi is an aliphatic amino acid) associates preferentially with the second PDZ
domain of SAP97 (SAP97(PDZ2)). To understand the structural basis of this
interaction, we have determined the crystal structures of wild-type and a
SAP97(PDZ2) variant in complex with an 18-mer C-terminal peptide (residues
890-907) of GluR-A and of two variant PDZ2 domains in unliganded state at
1.8-2.44 A resolutions. SAP97(PDZ2) folds to a compact globular domain
comprising six beta-strands and two alpha-helices, a typical architecture for
PDZ domains. In the structure of the peptide complex, only the last four
C-terminal residues of the GluR-A are visible, and align as an antiparallel
beta-strand in the binding groove of SAP97(PDZ2). The free carboxylate group and
the aliphatic side chain of the C-terminal leucine (Leu907), and the hydroxyl
group of Thr905 of the GluR-A peptide are engaged in essential class I PDZ
interactions. Comparison between the free and complexed structures reveals
conformational changes which take place upon peptide binding. The
betaAlpha-betaBeta loop moves away from the C-terminal end of alphaB leading to
a slight opening of the binding groove, which may better accommodate the peptide
ligand. The two conformational states are stabilized by alternative hydrogen
bond and coulombic interactions of Lys324 in betaAlpha-betaBeta loop with Asp396
or Thr394 in betaBeta. Results of in vitro binding and immunoprecipitation
experiments using a PDZ motif-destroying L907A mutation as well as the insertion
of an extra alanine residue between the C-terminal Leu907 and the stop codon are
also consistent with a 'classical' type I PDZ interaction between SAP97 and
GluR-A C-terminus.
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