Interaction networks within disease-associated Gα variants characterized by an integrative biophysical approach.

Activation of G proteins through nucleotide exchange initiates intracellular signaling cascades essential for life processes. Under normal conditions, nucleotide exchange is regulated by the formation of G protein-G protein-coupled receptor complexes. Single point mutations in the Gα subunit of G proteins bypass this interaction, leading to loss of function or constitutive gain of function, which is closely linked with the onset of multiple diseases.

Error mitigation in LPWAN systems: A study on the efficacy of Hamming-coded RPW.

Rotating Polarization Wave (RPW) is a novel Low Power Wide Area Networks (LPWAN) technology for robust connectivity and extended coverage area as compared to other LPWAN technologies such as LoRa and Sigfox when no error detection and correction is employed. Since, IoT and Machine-to-Machine (M2M) communication demand high reliability, RPW with error correction can significantly enhance the communication reliability for critical IoT and M2M applications. Therefore, this study investigates the performance of RPW with single bit error detection and correction using Hamming codes to avoid substantial overhead.

Visualizing the impact of disease-associated mutations on G protein-nucleotide interactions.

Activation of G proteins stimulates ubiquitous intracellular signaling cascades essential for life processes. Under normal physiological conditions, nucleotide exchange is initiated upon the formation of complexes between a G protein and G protein-coupled receptor (GPCR), which facilitates exchange of bound GDP for GTP, subsequently dissociating the trimeric G protein into its Gα and Gβγ subunits. However, single point mutations in Gα circumvent nucleotide exchange regulated by GPCR-G protein interactions, leading to either loss-of-function or constitutive gain-of-function.

Conserved Protein-Polymer Interactions across Structurally Diverse Polymers Underlie Alterations to Protein Thermal Unfolding.

Protein-polymer conjugates are widely used in many clinical and industrial applications, but lack of experimental data relating protein-polymer interactions to improved protein stability prevents their rational design. Advances in synthetic chemistry have expanded the palette of polymer designs, including development of nonlinear architectures, novel monomer chemical scaffolds, and control of hydrophobicity, but more experimental data are needed to transform advances in chemistry into next generation conjugates. Using an integrative biophysical approach, we investigated the molecular basis for polymer-based thermal stabilization of a human galectin protein, Gal3C, conjugated with polymers of linear and nonlinear architectures, different degrees of polymerization, and varying hydrophobicities.

Sodium is a negative allosteric regulator of the ghrelin receptor.

The functional properties of G protein-coupled receptors (GPCRs) are intimately associated with the different components in their cellular environment. Among them, sodium ions have been proposed to play a substantial role as endogenous allosteric modulators of GPCR-mediated signaling. However, this sodium effect and the underlying mechanisms are still unclear for most GPCRs.

Global insights into the fine tuning of human AAR conformational dynamics in a ternary complex with an engineered G protein viewed by NMR.

G protein-coupled receptor (GPCR) conformational plasticity enables formation of ternary signaling complexes with intracellular proteins in response to binding extracellular ligands. We investigate the dynamic process of GPCR complex formation in solution with the human A adenosine receptor (AAR) and an engineered G protein, mini-G. 2D nuclear magnetic resonance (NMR) data with uniform stable isotope-labeled AAR enabled a global comparison of AAR conformations between complexes with an agonist and mini-G and with an agonist alone.

Atomic-Scale View of Protein-PEG Interactions that Redirect the Thermal Unfolding Pathway of PEGylated Human Galectin-3.

PEGylation is a promising approach to address the central challenge of applying biologics, i.e., lack of protein stability in the demanding environment of the human body.

A New LoRa-like Transceiver Suited for LEO Satellite Communications.

LoRa is based on the chirp spread spectrum (CSS) modulation, which has been developed for low power and long-range wireless Internet of Things (IoT) communications. The structure of LoRa signals makes their decoding performance extremely sensitive to synchronization errors. To alleviate this constraint, we propose a modification of the LoRa physical layer, which we refer to as differential CSS (DCSS), associated with an original synchronization algorithm.

Structural biology of human GPCR drugs and endogenous ligands - insights from NMR spectroscopy.

G protein-coupled receptors (GPCRs) represent the largest class of "druggable" proteins in the human genome. For more than a decade, crystal structures and, more recently, cryoEM structures of GPCR complexes have provided unprecedented insight into GPCR drug binding and cell signaling. Nevertheless, structure determination of receptors in complexes with weakly binding molecules or complex polypeptides remains especially challenging, including for hormones, many of which have so far eluded researchers.

The conical shape of DIM lipids promotes infection of macrophages.

Phthiocerol dimycocerosate (DIM) is a major virulence factor of the pathogen (). While this lipid promotes the entry of into macrophages, which occurs via phagocytosis, its molecular mechanism of action is unknown. Here, we combined biophysical, cell biology, and modeling approaches to reveal the molecular mechanism of DIM action on macrophage membranes leading to the first step of infection.

Structure and dynamics of dynorphin peptide and its receptor.

Dynorphin is a neuropeptide involved in pain, addiction and mood regulation. It exerts its activity by binding to the kappa opioid receptor (KOP) which belongs to the large family of G protein-coupled receptors. The dynorphin peptide was discovered in 1975, while its receptor was cloned in 1993.

Structure and dynamics of G protein-coupled receptor-bound ghrelin reveal the critical role of the octanoyl chain.

Ghrelin plays a central role in controlling major biological processes. As for other G protein-coupled receptor (GPCR) peptide agonists, the structure and dynamics of ghrelin bound to its receptor remain obscure. Using a combination of solution-state NMR and molecular modeling, we demonstrate that binding to the growth hormone secretagogue receptor is accompanied by a conformational change in ghrelin that structures its central region, involving the formation of a well-defined hydrophobic core.