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

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

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 ...

EPFL2024

Computational drug development for membrane protein targets

Henning Paul-Julius Stahlberg, Pierre Vogel, Shuguang Yuan, Dongchun Ni, Babatunde Edukpe Ekundayo

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 ...

2024

Antibodies expand the scope of angiotensin receptor pharmacology

Patrick Daniel Barth, Shuhao Zhang

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 ...

2024

A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits

Mauro Pulin

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 ...

Nature Portfolio2024

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

Pengfei Xu, Sangwoo Kim

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 ...

Nature Portfolio2024

Ultraviolet Superradiance from Mega-Networks of Tryptophan in Biological Architectures

Majed Chergui, Katrin Elisabeth Oberhofer

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 ...

Amer Chemical Soc2024

Rules and mechanisms governing G protein coupling selectivity of GPCRs

Bruno Emanuel Ferreira De Sousa Correia, Pablo Gainza Cirauqui

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 ...

Cell Press2023

Unlocking Hidden Potential: Exploring the Complexities of Signaling in Immune Cell Activation to Optimize CAR Therapy

Mathieu Girardin

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 ...

EPFL2023

Towards Uncovering the Mechanisms of Electrophile Sensing and Signaling

Chloé Rogg

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 ...

EPFL2023

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

Louis Georges Baptiste Dumas, Matthieu François Marfoglia, Patrick Daniel Barth

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 ...

2023

Exploring the interplay of molecular pattern and valency for selective interactions at the bio-interface

Kaltrina Paloja

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, ...

EPFL2023

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

Philippe Renaud, Arnaud Bertsch, Clémentine Sophie Sarah Lipp

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 ...

ROYAL SOC CHEMISTRY2023

Rational design of protein switches: applications in synthetic biology and cancer immunotherapy

Sailan Shui

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 ...

EPFL2022

Computationally designed GPCR quaternary structures bias signaling pathway activation

Patrick Daniel Barth, Robert Everett Jefferson

Communication across membranes controls critical cellular processes and is achieved by receptors translating extracellular signals into selective cytoplasmic responses. While receptor tertiary structures can be readily characterized, receptor associations ...

Nature Research2022

Significance of Receptor Mobility in Multivalent Binding on Lipid Membranes

Maartje Martina Cornelia Bastings, Diana Kornelia Morzy

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 ...

Wiley-VCH Verlag GmbH2022

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

Yimon Aye, Pierre Alexander Miranda Herrera

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 ...

AMER CHEMICAL SOC2022

Method and system for determining intracellular mediators' activity

Horst Vogel, Philippe Renaud, Thamani Dahoun, Margaux Catherine Marie Duchamp, Marc Brugarolas Campillos

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 ...

2022

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

David Lyndon Emsley, Pierrick Berruyer, Andrea Bertarello

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 ...

AMER CHEMICAL SOC2022

Selective integrin targeting with DNA-based nanomaterials

Eva Eugene Kurisinkal

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 ...

EPFL2022

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

Dániel Kéri

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 ...

EPFL2021