PDZ Domains: Structural Modules for Protein Complex Assembly*

By A. Hung, M. Sheng. 2002

707 citations recorded by the source corpus.

PDZ domains 1 are modular protein interaction domains that play a role in protein targeting and protein complex assembly. Once termed Discs-large homology regions (DHRs) or GLGF repeats (after a conserved Gly-Leu-Gly-Phe sequence found within the domain), these domains of (cid:1) 90 amino acids are now primarily known by an acronym of the first three PDZ-containing proteins identified: the postsynaptic protein PSD-95/SAP90, the Drosophila septate junction protein Discs-large, and the tight junction protein ZO-1. Since their initial identification, PDZ and PDZ-like domains have been recognized in numerous proteins from organisms as diverse as bacteria, plants, yeast, metazoans, and Drosophila (1). In fact, they are among the commonest protein domains repre-sented in sequenced genomes. Analysis of the human, Drosophila , and Caenorhabditis elegans genomes estimates the presence of 440 PDZ domains in 259 different proteins, 133 PDZ domains in 86 proteins, and 138 PDZ domains in 96 proteins, respectively (2). The structural features of PDZ domains allow them to mediate specific protein-protein interactions that underlie the assembly of large protein complexes involved in signaling or subcellular trans- port. Not surprisingly, disrupting these interactions can play a role in human diseases. Mutations in a gene encoding harmonin, a PDZ-containing protein, cause Usher syndrome type 1C, an auto-somal recessive disorder characterized by congenital sensorineural deafness, vestibular dysfunction, and blindness (3–5). This was the first mutation in a PDZ-encoding gene linked to a human disease. Subsequently, mutations in the periaxin gene, which also encodes

Subfields: Cell Biology, Molecular Biology, Neurology

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Citations in the corpus

Revealing evolutionary constraints on proteins through sequence analysis (2018, background): “ protein properties [11,20{22], including the emergence of allostery [23{29]. Thus motivated, we begin by building an elastic-network model [11,20] for a well-studied PDZ protein domain (Fig. 1(a,b)) [30,31] and computing the relationship between its \sequence" and the energetic cost of a funct”
International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors (2010, background): “The carboxyl tail of the two receptors contain consensus sites for casein kinase 1 , casein kinase II, and protein kinase C as well as postsynaptic density 95/disc-large/zona occludens binding domains that may participate in membrane localization and trafficking (Hung and Sheng, 2002).”
The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance (2006, neutral): “PDZ domains are most often found in combination with other protein interaction domains (for instance, SH3, PTB, WW), participating in complexes that facilitate signaling or determine the localization of receptors [126–128].”
The exocyst complex in polarized exocytosis. (2004, positive): “, 2003), a member of the membrane-associated guanylate kinase (MAGUK) family that has been shown to participate in the assembly of synaptic signaling complexes at excitatory synapses (Fang and Zhang, 2002; Hung and Sheng, 2002).”
Toxic proteins released from mitochondria in cell death (2004, background): “PDZ domains (postsynaptic density protein, disc large tumour suppressor and Zo-1 tight junction protein), generally implicated in protein–protein interactions, can be subdivided into different classes based on their binding specificities (Harris and Lim, 2001; Hung and Sheng, 2002).”
Functional dynamics of PDZ binding domains: a normal-mode analysis. (2005, background): “To explore the different role of the PDZ topology with respect to its chemistry in determining the binding movements, we have shifted from the CHARMM force-field, where both topology and full chemical details are taken into account, to the ANM description in its Cβ version, which deals only with the”
Graphical Models of Residue Coupling in Protein Families (2008, background): “, to identify protein-specific motifs [2], [24], map allosteric pathways [16], [36], predict protein structures [10], [27], [34] and interactions [13], [29], and design new peptide vaccines [17].”
Graphical models of protein–protein interaction specificity from correlated mutations and interaction data (2009, background): “34,35 Figure 3 shows a representative three dimensional structure of a PDZ domain interacting with a ligand.”
Graphical models of residue coupling in protein families (2005, background): “Knowing which pairs (or sets) of residues are coupled in a protein family aids our understanding of many important processes, e.g., conformational change and protein folding [21, 24], signaling [26], protein-protein interaction, and even protein complex assembly [13].”
Identification and phylogenetic analysis of Dictyostelium discoideum kinesin proteins (2003, positive): “PDZ domains play important roles in the transport, localization and assembly of supramolecular signalling complexes [39].”