title: Structures and target recognition modes of PDZ domains: recurring themes and emerging pictures.
abstract: PDZ domains are highly abundant protein-protein interaction modules and are often found in multidomain scaffold proteins. PDZ-domain-containing scaffold proteins regulate multiple biological processes, including trafficking and clustering receptors and ion channels at defined membrane regions, organizing and targeting signalling complexes at specific cellular compartments, interfacing cytoskeletal structures with membranes, and maintaining various cellular structures. PDZ domains, each with ~90-amino-acid residues folding into a highly similar structure, are best known to bind to short C-terminal tail peptides of their target proteins. A series of recent studies have revealed that, in addition to the canonical target-binding mode, many PDZ-target interactions involve amino acid residues beyond the regular PDZ domain fold, which we refer to as extensions. Such extension sequences often form an integral structural and functional unit with the attached PDZ domain, which is defined as a PDZ supramodule. Correspondingly, PDZ-domain-binding sequences from target proteins are frequently found to require extension sequences beyond canonical short C-terminal tail peptides. Formation of PDZ supramodules not only affords necessary binding specificities and affinities demanded by physiological functions of PDZ domain targets, but also provides regulatory switches to be built in the PDZ-target interactions. At the 20th anniversary of the discovery of PDZ domain proteins, we try to summarize structural features and target-binding properties of such PDZ supramodules emerging from studies in recent years.
authors.affiliation: *Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001665:Binding Sites; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D054731:PDZ Domains; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D020080:Tandem Repeat Sequences
chemical_list: D007473:Ion Channels; D011956:Receptors, Cell Surface