Publications related to G protein

A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits

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

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

The role of LRRK2 in lung adenocarcinoma

Aspasia Gkasti

Lung cancer is the leading cause of cancer-related deaths worldwide and the most common lung cancer subtype is lung adenocarcinoma (LUAD). Frequently mutated genes involve activating mutations in KRAS and loss of function mutations in TP53. LUADs primarily ...

EPFL2024

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

Mahdi Hijazi

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

Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Anthony Marchand

Proteins are foundational biomolecules of life playing a crucial role in a myriad of biological processes. Their function often requires interplay with other biomolecules, including proteins themselves. Protein-protein interactions (PPIs) are essential for ...

EPFL2024

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

Pauline Franz

DNA damage signaling following DNA double-strand breaks (DSBs) involves numerous regulating proteins, which dynamically recognize ('read') and alter ('write' or 'erase') histone post-translational modifications (PTMs). Among these PTMs, the ubiquitin syste ...

EPFL2024

First paleoproteome study of fossil fish otoliths and the pristine preservation of the biomineral crystal host

Anders Meibom, Jaroslaw Hubert Stolarski, Jinming Guo

Otoliths are calcium carbonate components of the stato-acoustical organ responsible for hearing and maintenance of the body balance in teleost fish. During their formation, control over, e.g., morphology and carbonate polymorph is influenced by complex ins ...

Nature Portfolio2023

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

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

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

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

Impact of phylogeny on structural contact inference from protein sequence data

Anne-Florence Raphaëlle Bitbol, Umberto Lupo, Nicola Dietler

Local and global inference methods have been developed to infer structural contacts from multiple sequence alignments of homologous proteins. They rely on correlations in amino acid usage at contacting sites. Because homologous proteins share a common ance ...

ROYAL SOC2023

Refining S-acylation: Structure, regulation, dynamics, and therapeutic implications

Françoise Gisou van der Goot Grunberg, Muhammad Umair Anwar

S-acylation is one of the most frequent posttranslational modifications that regulates diverse cellular processes. Anwar and van der Goot discuss the complexity and disease implications of this highly regulated reversible lipidation. ...

Rockefeller University Press2023

SLC25A46 promotes mitochondrial fission and mediates resistance to lipotoxic stress in INS-1E insulin-secreting cells

Loïc Dayon, Andreas Wiederkehr

Glucose sensing in pancreatic D-cells depends on oxidative phosphorylation and mitochondria-derived signals that promote insulin secretion. Using mass spectrometry-based phosphoproteo-mics to search for downstream effectors of glucose-dependent signal tran ...

COMPANY BIOLOGISTS LTD2023

Structure of a membrane-bound menaquinol:organohalide oxidoreductase

Christof Holliger, Henning Paul-Julius Stahlberg, Julien Maillard, Dongchun Ni, Babatunde Edukpe Ekundayo, Lorenzo Cimmino

Organohalide-respiring bacteria are key organisms for the bioremediation of soils and aquifers contaminated with halogenated organic compounds. The major players in this process are respiratory reductive dehalogenases, corrinoid enzymes that use organohali ...

Nature Research2023

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

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

AMP-activated Protein Kinase (AMPK): New molecular insights and novel downstream targets

Katyayanee Neopane

AMP-activated Protein Kinase (AMPK) is a central regulator of energy homeostasis and a promising drug target for metabolic disorders. It exists as complexes of three subunits, a catalytic alpha, and two regulatory beta and gamma subunits. The regulation of ...

EPFL2022

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

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

Sphingolipids accumulate in aged muscle, and their reduction counteracts sarcopenia

Johan Auwerx, Davide D'Amico, Tanes Imamura de Lima, Qi Wang, Sébastien Robert Victor Herzig, Maroun Bou Sleiman, Martin Rainer Wohlwend, Peiling Luan, Pirkka-Pekka Untamo Laurila, Barbara Moreira Crisol

Age-related muscle dysfunction and sarcopenia are major causes of physical incapacitation in older adults and currently lack viable treatment strategies. Here we find that sphingolipids accumulate in mouse skeletal muscle upon aging and that both genetic a ...

2022

Protein Engineering for Personalized therapy and diagnosis

Lixia Wei

Protein Engineering, especially protein post-translational modification (PTM), ex-tends proteomes in a more complex way than one can expect from analysis of their encod-ing genomes. It can activate or deactivate certain catalytic functions, add new desired ...

EPFL2022