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Plakin proteins form connections that link the cell membrane to the intermediate filament cytoskeleton. Their interactions are mediated by a highly conserved linker domain through an unresolved mechanism. Here analysis of the human periplakin linker domain structure reveals a bi-lobed module transected by an electropositive groove. Key basic residues within the periplakin groove are vital for co-localization with vimentin in human cells and compromise direct binding which also requires acidic residues D176 and E187 in vimentin. We propose a model whereby basic periplakin linker domain residues recognize acidic vimentin side chains and form a complementary binding groove. The model is shared amongst diverse linker domains and can be used to investigate the effects of pathogenic mutations in the desmoplakin linker associated with arrhythmogenic right ventricular cardiomyopathy. Linker modules either act solely or collaborate with adjacent plakin repeat domains to create strong and adaptable tethering within epithelia and cardiac muscle., Odinstova, Mohammed, Trieber et al. use structure-based mutagenesis to identify key residues in human periplakin and desmoplakin linker modules required for co-localization with vimentin intermediate filaments. They show that vimentin D176 and E187 are required for direct binding with the periplakin linker.

Gold, silver, and copper small nanoparticles (NPs), with average size ≈2 nm, are synthesized and afterward protected with l- and d-cysteine, demonstrating emergence of chiroptical activity in the wavelength range of 250-400 nm for all three metals with respect to the bare nanoparticles and ligands alone. Silver-cysteine (Ag-Cys) NPs display the higher anisotropy factor, whereas gold-cysteine (Au-Cys) NPs show optical and chiroptical signatures slightly more displaced to the visible range. A larger number of circular dichroism (CD) bands with smaller intensity, as compared to gold and silver, is observed for the first time for copper-cysteine (Cu-Cys) NPs. The manifestation of optical and chiroptical responses upon cysteine adsorption and the differences between the spectra corresponding to each metal are mainly dictated by the metal-ligand interface, as supported by a comparison with calculations of the oscillatory and rotatory strengths based on time-dependent density functional theory, using a metal-ligand interface motif model, which closely resembles the experimental absorption and CD spectra. These results are useful to demonstrate the relevance of the interface between chiral ligands and the metal surfaces of Au, Ag, and Cu NPs, and provide evidence and further insights into the origin of the transfer mechanisms and induction of extrinsic chirality.

We exploit the immobilization of proteins by size-selected atomic gold clusters to examine the plakin domain of desmoplakin (PD), a human desmosomal protein that is mutated in severe skin diseases and cardiomyopathy, using atomic force microscopy (AFM) in the liquid phase. Contact mode AFM indicates that the PD does not establish a covalent bond size-selected gold nanocluster supported on a graphite substrate, but tapping mode AFM images indicate enhanced weak adsorption. The protein dimensions obtained are compared with predicted values based on electron microscopy, small-angle X-ray scattering (SAXS) and X-ray crystallographic studies.

The immobilization of individual biological molecules by metal nanoparticles requires that the particles themselves be immobilized. We introduce a new technique for immobilization of gold clusters based on their binding to small tunnels in a graphite support, themselves created by the implantation of small clusters. These tunnels are shown to perform as more effective cluster immobilization sites than point defects on the surface of graphite. The method is tested with atomic force microscopy (AFM) (both contact and noncontact mode) scanning. Size-selected clusters with 923, 561, 309, and 147 atoms have been immobilized and imaged with high-resolution, noncontact AFM.