title: Tandem PDZ repeats in glutamate receptor-interacting proteins have a novel mode of PDZ domain-mediated target binding.
abstract: The interaction of the glutamate receptor subunits 2 and 3 (GluR2/3) with multi-PDZ domain glutamate receptor-interacting protein (GRIP) is important for the synaptic trafficking and clustering of the receptors. Binding of GluR2/3 to GRIP requires both the fourth and fifth PDZ domains (PDZ4 and PDZ5) to be covalently linked, although only one PDZ domain is directly involved in binding to the receptor tail. To elucidate the molecular basis of this mode of PDZ domain-mediated target recognition, we solved the solution structures of the PDZ45 tandem and the isolated PDZ4 of GRIP. The two PDZ domains form a compact structure with a fixed interdomain orientation. The interdomain packing and the stable folding of both PDZ domains require a short stretch of amino acids N-terminal to PDZ4 and a conserved linker connecting PDZ4 and PDZ5. PDZ4 contains a deformed aB-bB groove that is unlikely to bind to carboxyl peptides. Instead, the domain stabilizes the structure of PDZ5.
authors.affiliation: Department of Biochemistry, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.forename: Yawei
authors.initials: Y
authors.lastname: Shi
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D002352:Carrier Proteins; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins