The Dual PDZ Domain from Postsynaptic Density Protein 95 Forms a Scaffold with Peptide Ligand.

PSD-95 is a member of the membrane-associated guanylate kinase class of proteins that forms scaffolding interactions with partner proteins, including ion and receptor channels. PSD-95 is directly implicated in modulating the electrical responses of excitable cells. The first two PSD-95/disks large/zona occludens (PDZ) domains of PSD-95 have been shown to be the key component in the formation of channel clusters. We report crystal structures of this dual domain in both apo- and ligand-bound form: thermodynamic analysis of the ligand association and small-angle x-ray scattering of the dual domain in the absence and presence of ligands. These experiments reveal that the ligated double domain forms a three-dimensional scaffold that can be described by a space group. The concentration of the components in this study is comparable with those found in compartments of excitable cells such as the postsynaptic density and juxtaparanodes of Ranvier. These in vitro experiments inform the basis of the scaffolding function of PSD-95 and provide a detailed model for scaffold formation by the PDZ domains of PSD-95.

Criteria for liquid crystal formation in 5-alkoxy-, 5-alkylamino-, and 5-alkanoyl-tropolone complexes of transition metals (Cu(II), Zn(II), Ni(II), Co(II), UO(2)(VI), VO(IV)). The first uranium metallomesogen. Crystal structure of bis(5-hexadecyloxytropolonato)copper(II).

The mesophase properties of bis(5-alkoxytropolonato)copper(II) complexes are reported and interpreted in terms of d-layer spacings, which indicate considerable intertwining of the alkyl chains. The mesogenic properties depend on the nature of the 5-substituent: to be mesogenic, it must be alkoxy with n > 8, and may not be 5-alkanoyl or 5-alkylamino. The nature of the metal is also important: to be mesogenic, it may be Cu(II) or UO(2)(VI) but not Ni(II), Zn(II), Co(II), or VO(IV). The crystal structure of bis(5-hexadecyloxytropolonato)copper(II) shows how, even in the crystalline state, molecular packing is dominated by the interactions between alkyl chains, together with copper-oxygen interactions. In the Cu(II) complexes, strong interactions occur between Cu atoms and O atoms of neighboring molecules. These are stronger than alkyl-alkyl interactions and therefore dominate alkyl-alkyl interactions between neighbors which otherwise govern the possibility and nature of mesogenic properties. The Cu.O interactions disrupt alkyl-alkyl chain interactions enough to produce a mesophase; such interactions do not obtain in the T(d)() Zn(II) and Co(II) complexes, and indeed, these complexes are not mesogenic. Likewise, alkyl chain interactions by the oxygens of the UO(2)(VI) lead to a mesophase, and U constitutes the heaviest metal ever placed into a mesogenic molecule. In the case of VO(IV), analogous synthetic steps from VOSO(4) led to a new series of binuclear complexes [(VO)(2)(SO(4))(5-alkoxytropoloato)(2)].