PDZ domains, originally described as conserved structural elements in the 95-kDa post-synaptic density protein (PSD-95), 1 the Drosophila tumor suppressor discs-large, and the tight junction protein zonula occludens-1 (ZO-1), are contained in a large and diverse set of proteins (1-3). In general, PDZ domain-containing proteins appear to assemble various functional entities, including ion channels and other transmembrane receptors, at specialized subcellular sites such as epithelial cell tight junctions, neuromuscular junctions, and postsynaptic densities of neurons. These clustering and localization effects have important biological implications. For example, the membrane-associated guanylate kinase, PSD-95, segregates the N-methyl D-aspartate (NMDA) receptor and the Shaker potassium channel to the post-synaptic density of neurons (4). In another illustration, the aggregation of various components of the fruit fly visual system by the multi-PDZ protein INAD greatly enhances the efficiency of this signaling cascade (5). Another compelling case is the use of several PDZ domaincontaining proteins in the appropriate basolateral localization of the LET-23 receptor tyrosine kinase of Caenorhabditis elegans (6). This kinase is required for vulval development, and mutations in these PDZ domain-containing proteins result in the subcellular mislocalization of the LET-23 protein and a lack of vulval differentiation. Together with many other examples, these studies indicate that PDZ domains are important intracellular assembly and localization cofactors in diverse signaling pathways.PDZ domains recognize three different types of ligands, with two of these interactions showing specificity for peptides at the extreme carboxyl termini of proteins (7-9). Type I and type II PDZ domains recognize carboxyl-terminal peptides with the consensus sequence Thr/Ser-X-Phe/Val/Ala-COOH or Phe/Tyr-X-Phe/Val/Ala-COOH, respectively. Interestingly, a third type of PDZ domain-ligand interaction involves the recognition of an internal peptide sequence. Structural analyses of these three types of PDZ interactions have illuminated the mechanisms of ligand recognition. For example, the crystal structure of a type I PDZ domain from PSD-95 showed that a 4-residue carboxylterminal peptide interacts with the protein via an antiparallel main chain association with a ␤ strand, and the terminal carboxylate is inserted into a conserved "carboxylate binding loop" (10, 11). The crystal structure of a PDZ domain from human CASK revealed the nature of interactions mediated by type II motifs (12). In both domain types, the peptide formed a new antiparallel ␤ strand in the PDZ domain structure, and the overall conformations of the two interactions were similar. However, there were significant differences in side chain contacts that could account for the different ligand specificities of the two domain types. Finally, the interaction between a PDZ domain of syntrophin and a PDZ domain of the neuronal nitric oxide synthase has been examined by x-ray and NMR analy...

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A new series of polynuclear superalkali cations YLi(3)(+) (Y = CO(3), SO(3), SO(4), O(4), and O(5)) has been created when the central group is surrounded by alkali atoms. The structural characteristics and stabilities of these systems are provided on the basis of ab initio methods. In the lowest-energy structure of the CO(3)Li(3)(+), SO(3)Li(3)(+), and SO(4)Li(3)(+) cations, the central Y (Y = CO(3), SO(3), and SO(4)) group features a slight distortion. The global minima of O(4)Li(3)(+) and O(5)Li(3)(+) are of the forms O(2)(-)(Li(+))(3)O(2)(-) and O(2)(-)(Li(+))(3)O(3)(-), respectively, both of which contain two monovalent ion units. The structural integrity of the central Y group and the arrangement of the lithium ligands are two influencing factors on the vertical electron affinities (EA(vert)) for the YLi(3)(+) species. The YLi(3)(+) cation, with its lithium ligands being distributed evenly or far from each other, tends to exhibit a low EA(vert) value, whereas a greater extent of cleavage of the central Y group leads to a higher EA(vert) value and even makes some species lose their superalkali nature.