Deciphering the Arginine-Binding Preferences at the Substrate-Binding Groove of Ser/Thr Kinases by Computational Surface Mapping

Protein kinases are key signaling enzymes that catalyze the transfer of γ-phosphate from an ATP molecule to a phospho-accepting residue in the substrate. Unraveling the molecular features that govern the preference of kinases for particular residues flanking the phosphoacceptor is important for understanding kinase specificities toward their substrates and for designing substrate-like peptidic inhibitors. We applied ANCHORSmap, a new fragment-based computational approach for mapping amino acid side chains on protein surfaces, to predict and characterize the preference of kinases toward Arginine binding. We focus on positions P−2 and P−5, commonly occupied by Arginine (Arg) in substrates of basophilic Ser/Thr kinases. The method accurately identified all the P−2/P−5 Arg binding sites previously determined by X-ray crystallography and produced Arg preferences that corresponded to those experimentally found by peptide arrays. The predicted Arg-binding positions and their associated pockets were analyzed in terms of shape, physicochemical properties, amino acid composition, and in-silico mutagenesis, providing structural rationalization for previously unexplained trends in kinase preferences toward Arg moieties. This methodology sheds light on several kinases that were described in the literature as having non-trivial preferences for Arg, and provides some surprising departures from the prevailing views regarding residues that determine kinase specificity toward Arg. In particular, we found that the preference for a P−5 Arg is not necessarily governed by the 170/230 acidic pair, as was previously assumed, but by several different pairs of acidic residues, selected from positions 133, 169, and 230 (PKA numbering). The acidic residue at position 230 serves as a pivotal element in recognizing Arg from both the P−2 and P−5 positions

Strong light-matter coupling in two-dimensional atomic crystals

Two dimensional (2D) atomic crystals of graphene, and transition metal dichalcogenides have emerged as a class of materials that show strong light-matter interaction. This interaction can be further controlled by embedding such materials into optical microcavities. When the interaction is engineered to be stronger than the dissipation of light and matter entities, one approaches the strong coupling regime resulting in the formation of half-light half-matter bosonic quasiparticles called microcavity polaritons. Here we report the evidence of strong light-matter coupling and formation of microcavity polaritons in a two dimensional atomic crystal of molybdenum disulphide (MoS2) embedded inside a dielectric microcavity at room temperature. A Rabi splitting of 46 meV and highly directional emission is observed from the MoS2 microcavity owing to the coupling between the 2D excitons and the cavity photons. Realizing strong coupling effects at room temperature in a disorder free potential landscape is central to the development of practical polaritonic circuits and switches.Comment: 25 pages, 7 figure

Interdependence between transportation system and power distribution system: a comprehensive review on models and applications

The rapidly increasing penetration of electric vehicles in modern metropolises has been witnessed during the past decade, inspired by financial subsidies as well as public awareness of climate change and environment protection. Integrating charging facilities, especially high-power chargers in fast charging stations, into power distribution systems remarkably alters the traditional load flow pattern, and thus imposes great challenges on the operation of distribution network in which controllable resources are rare. On the other hand, provided with appropriate incentives, the energy storage capability of electric vehicle offers a unique opportunity to facilitate the integration of distributed wind and solar power generation into power distribution system. The above trends call for thorough investigation and research on the interdependence between transportation system and power distribution system. This paper conducts a comprehensive survey on this line of research. The basic models of transportation system and power distribution system are introduced, especially the user equilibrium model, which describes the vehicular flow on each road segment and is not familiar to the readers in power system community. The modelling of interdependence across the two systems is highlighted. Taking into account such interdependence, applications ranging from long-term planning to short-term operation are reviewed with emphasis on comparing the description of traffic-power interdependence. Finally, an outlook of prospective directions and key technologies in future research is summarized.fi=vertaisarvioitu|en=peerReviewed

FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells

Little is known about whether autophagic mechanisms are active in hematopoietic stem cells (HSCs) or how they are regulated. FIP200 (200-kDa FAK-family interacting protein) plays important roles in mammalian autophagy and other cellular functions, but its role in hematopoietic cells has not been examined. Here we show that conditional deletion of FIP200 in hematopoietic cells leads to perinatal lethality and severe anemia. FIP200 was cell-autonomously required for the maintenance and function of fetal HSCs. FIP200-deficient HSC were unable to reconstitute lethally irradiated recipients. FIP200 ablation did not result in increased HSC apoptosis, but it did increase the rate of HSC proliferation. Consistent with an essential role for FIP200 in autophagy, FIP200-null fetal HSCs exhibited both increased mitochondrial mass and reactive oxygen species. These data identify FIP200 as a key intrinsic regulator of fetal HSCs and implicate a potential role for autophagy in the maintenance of fetal hematopoiesis and HSCs