Energy Transfer into Period-Tripled States in Coupled Electromechanical Modes at Internal Resonance

Efficient energy transfer often occurs between oscillation modes in a resonator when they are tuned to internal resonance. We design the eigenfrequencies of two vibrational modes of an electromechanical resonator to be close to a ratio of 3:1 and demonstrate that the energy supplied to the upper mode can be controllably transferred to the lower mode. With the lower mode vibrating with a period tripled that of the upper mode, the discrete time-translation symmetry imposed by the periodic drive is broken. The lower mode settles into one of three stable period-tripled states with different phases. This channel for energy transfer from the upper mode can be turned on or off without changing system parameters. When the upper mode itself becomes multistable under strong resonant or parametric drive, additional sets of coexisting period-tripled states emerge in the lower mode. In the latter case, we measure a total of 6 coexisting vibration states with identical amplitude but phases differing by $\pi$/3. Excitation of coexisting states with three different phases could open new opportunities in designing mechanical memory based on ternary logic. Coupled resonators with period-tripled states can also be used to model complex interacting systems with spin equals one

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

Bioinformatic Analysis and Post-Translational Modification Crosstalk Prediction of Lysine Acetylation

Recent proteomics studies suggest high abundance and a much wider role for lysine acetylation (K-Ac) in cellular functions. Nevertheless, cross influence between K-Ac and other post-translational modifications (PTMs) has not been carefully examined. Here, we used a variety of bioinformatics tools to analyze several available K-Ac datasets. Using gene ontology databases, we demonstrate that K-Ac sites are found in all cellular compartments. KEGG analysis indicates that the K-Ac sites are found on proteins responsible for a diverse and wide array of vital cellular functions. Domain structure prediction shows that K-Ac sites are found throughout a wide variety of protein domains, including those in heat shock proteins and those involved in cell cycle functions and DNA repair. Secondary structure prediction proves that K-Ac sites are preferentially found in ordered structures such as alpha helices and beta sheets. Finally, by mutating K-Ac sites in silico and predicting the effect on nearby phosphorylation sites, we demonstrate that the majority of lysine acetylation sites have the potential to impact protein phosphorylation, methylation, and ubiquitination status. Our work validates earlier smaller-scale studies on the acetylome and demonstrates the importance of PTM crosstalk for regulation of cellular function

An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation

The exocyst/aPKC complex controls the spatiotemporal activation of the kinases JNK and ERK at the leading edge of migrating cells and thereby controls the dynamic behaviour of the adhesion protein paxillin during cell migration

Structure-Specific Recognition Protein 1 Facilitates Microtubule Growth and Bundling Required for Mitosis▿†

Tight regulation of microtubule (MT) dynamics is essential for proper chromosome movement during mitosis. Here we show, using mammalian cells, that structure-specific recognition protein 1 (SSRP1) is a novel regulator of MT dynamics. SSRP1 colocalizes with the spindle and midbody MTs, and associates with MTs both in vitro and in vivo. Purified SSRP1 facilitates tubulin polymerization and MT bundling in vitro. Knockdown of SSRP1 inhibits the growth of MTs and leads to disorganized spindle structures, reduction of K-fibers and midbody fibers, disrupted chromosome movement, and attenuated cytokinesis in vivo. These results demonstrate that SSRP1 is crucial for MT growth and spindle assembly during mitosis