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- Title
Crystal structure of the second PDZ domain of SAP97 in complex with a GluR-A C-terminal peptide.
- Authors
von Ossowski, Ingemar; Oksanen, Esko; von Ossowski, Lotta; Chunlin Cai; Sundberg, Maria; Goldman, Adrian; Keinänen, Kari
- Abstract
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-φ-COOH where φ is an aliphatic amino acid) associates preferentially with the second PDZ domain of SAP97 (SAP97PDZ2). To understand the structural basis of this interaction, we have determined the crystal structures of wild-type and a SAP97PDZ2 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 Å resolutions. SAP97PDZ2 folds to a compact globular domain comprising six β-strands and two α-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 β-strand in the binding groove of SAP97PDZ2. 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 βΑ−βΒ loop moves away from the C-terminal end of αB 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 βΑ−βΒ loop with Asp396 or Thr394 in βΒ. 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.
- Subjects
PEPTIDES; MOLECULAR structure; NEURAL transmission; SYNAPSES; LIGANDS (Biochemistry); HYDROGEN bonding; CRYSTALS
- Publication
FEBS Journal, 2006, Vol 273, Issue 22, p5219
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2006.05521.x