The role of metal ions in G protein-coupled receptor signalling and drug discovery

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The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learni ...

G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often l ...

Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly mani ...

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic developmen ...

Networks of tryptophan (Trp)& horbar;an aromatic amino acid with strong fluorescence response & horbar;are ubiquitous in biological systems, forming diverse architectures in transmembrane proteins, cytoskeletal filaments, subneuronal elements, photorecepto ...

G protein-coupled receptors (GPCRs) convert extracellular stimuli into intracellular signaling by coupling to heterotrimeric G proteins of four classes: Gi/o, Gq, Gs, and G12/13. However, our understanding of the G protein selectivity of GPCRs is incomplet ...

Chimeric antigen receptors (CARs) are synthetic, transmembrane proteins that trigger immune cell signaling following their engagement. They have been first utilized in T cells and later in natural killer (NK) cells to redirect their cytotoxicity toward a s ...

Native reactive electrophile species (RES) such as 4-hydroxynonenal (HNE) act as cellular signals through covalent modification of kinetically-privileged electrophile sensor proteins. Research efforts in the field focus mainly on identifying these sensor p ...

The present invention relates to variants of the GAIN domain (G-protein-coupled receptor autoproteolysis-inducing domain) of an adhesion G protein-coupled receptor (ADGRG), such as a GAIN domain variant comprising or consisting of the amino acid sequence o ...

Cell-cell communication is fundamental for immune balance. Multivalent interactions of surface receptors at immune interfaces drive specific communication, with stimulatory and inhibitory signals guiding the immune outcome. Notably, the valency, affinity, ...

The understanding of cell-cell and cell-matrix interactions via receptor and ligand binding relies on our ability to study the very first events of their contact. Of particular interest is the interaction between a T cell receptor and its cognate peptide-m ...

Synthetic biology aims to engineer cells as miniature biological devices to sense, process, and respond to exogenous stimuli. Protein switches are designed to sense and respond to various molecular queues in a fast and specific manner, which fits the requi ...

Numerous key biological processes rely on the concept of multivalency, where ligands achieve stable binding only upon engaging multiple receptors. These processes, like viral entry or immune synapse formation, occur on the diffusive cellular membrane. One ...

Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are under active debate. However, in our opinion, it is becoming increasingly likely that electrophiles can rewi ...

A method for determining the presence of a molecule coupled to the cytoplasmic side of a cellular membrane is disclosed. The method is implemented in a microfluidic setting and is particularly suitable for determining the presence and/or the activity of a ...

The determination of intracellular drug concentrations can provide a better understanding of the drug function and efficacy. Ideally, this should be performed nondestructively, with no modification of either the drug or the target, and with the capability ...

Targeting cells specific to type and state remains a challenge in developing effective therapies, sensitive diagnostics, also robust and versatile tissue engineering. A promising strategy is to focuses on improving the inherent selectivity of the targeting ...

G protein-coupled receptors (GPCRs) are 7-transmembrane alpha-helical integral membrane proteins on which cells heavily rely to receive information regarding their external environment. These receptors are able to transfer information to intracellular down ...

Glycosphingolipids are important components of the plasma membrane where they modulate the activities of membrane proteins including signalling receptors. Glycosphingolipid synthesis relies on competing reactions catalysed by Golgi-resident enzymes during ...

The role of metal ions in G protein-coupled receptor signalling and drug discovery

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From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Computational drug development for membrane protein targets

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Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development

Ultraviolet Superradiance from Mega-Networks of Tryptophan in Biological Architectures

Rules and mechanisms governing G protein coupling selectivity of GPCRs

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Variants of the gain domain of adhesion g protein-coupled receptors

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Microfluidic device combining hydrodynamic and dielectrophoretic trapping for the controlled contact between single micro-sized objects and application to adhesion assays

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Significance of Receptor Mobility in Multivalent Binding on Lipid Membranes

Hitting the Bullseye: Endogenous Electrophiles Show Remarkable Nuance in Signaling Regulation

Method and system for determining intracellular mediators' activity

In-Cell Quantification of Drugs by Magic-Angle Spinning Dynamic Nuclear Polarization NMR

Selective integrin targeting with DNA-based nanomaterials

Reprogramming G Protein-Coupled Receptor Structure, Function And Signaling By Computational Design

Golgi maturation-dependent glycoenzyme recycling controls glycosphingolipid biosynthesis and cell growth via GOLPH3