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Concept

G beta-gamma complex

Publications associées (24)

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

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

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

Structure of a membrane-bound menaquinol:organohalide oxidoreductase

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

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

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

Investigation of physiological roles of AMPK-activated protein kinase y3

Philipp Jurijvic Rhein

Clinical trials have shown that direct activators of an evolutionary-conserved metabolic sensor, AMP-activated protein kinase (AMPK), are beneficial in preventing/treating a range of metabolic disorders, including type 2 diabetes. These activators, includi ...

EPFL2021

Low-energy electron holography imaging of conformational variability of single-antibody molecules from electrospray ion beam deposition

Klaus Kern, Stephan Rauschenbach, Sabine Abb, Sven Alexander Szilagyi, Hannah Julia Ochner

Imaging of proteins at the single-molecule level can reveal conformational variability, which is essential for the understanding of biomolecules. To this end, a biologically relevant state of the sample must be retained during both sample preparation and i ...

National Academy of Sciences2021

Morphogenesis Guided by 3D Patterning of Growth Factors in Biological Matrices

Matthias Lütolf, Nicolas Antoine Vincent Broguiere

Three-dimensional (3D) control over the placement of bioactive cues is fundamental to understand cell guidance and develop engineered tissues. Two-photon patterning (2PP) provides such placement at micro- to millimeter scale, but nonspecific interactions b ...

Wiley-V C H Verlag Gmbh2020

The Clustering of mApoE Anti-Amyloidogenic Peptide on Nanoparticle Surface Does Not Alter Its Performance in Controlling Beta-Amyloid Aggregation

Francesco Stellacci, Paulo Henrique Jacob Silva

The deposition of amyloid-beta (A beta) plaques in the brain is a significant pathological signature of Alzheimer's disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect o ...

2020

Nested oscillations and brain connectivity during sequential stages of feature-based attention

Gijs Plomp, David Pascucci

Brain mechanisms of visual selective attention involve both local and network-level activity changes at specific oscillatory rhythms, but their interplay remains poorly explored. Here, we investigate anticipatory and reactive effects of feature-based atten ...

2020

Computational pipeline to probe NaV1.7 gain-of-function variants in neuropathic painful syndromes

Stefano Zamuner

Applications of machine learning and graph theory techniques to neuroscience have witnessed an increased interest in the last decade due to the large data availability and unprecedented technology developments. Their employment to investigate the effect of ...

NATURE RESEARCH2020

Co-expression of CCT subunits hints at TRiC assembly

Oksana Andrei Sergeeva

The eukaryotic cytosolic chaperonin, t-complex polypeptide 1 (TCP-1) ring complex or TRiC, is responsible for folding a tenth of the proteins in the cell. TRiC is a double-ringed barrel with each ring composed of eight different CCT (chaperonin containing ...

2019

Association of Both Inhibitory and Stimulatory G alpha Subunits Implies Adenylyl Cyclase 5 Deactivation

Ursula Röthlisberger, Siri Camee van Keulen, Daniele Narzi

Adenylyl cyclase (AC) generates cyclic AMP required for a variety of cellular functions, and its regulation plays a major role in cellular signal transduction in eukaryotes and prokaryotes. All membrane-bound AC isoforms in eukaryotes can be activated by s ...

AMER CHEMICAL SOC2019

Exploitation of Unconventional Electrophiles in Enantioselective Pd(0)-Catalyzed C-H Functionalizations

Nicolai Cramer, Daria Grosheva

Asymmetric metal-catalyzed C-H functionalization is a powerful strategy for the rapid generation of complex target molecules from simple precursors. While aryl (pseudo) halides have been used as electrophilic substrates in enantioselective Pd(0)-catalyzed ...

2019

SNAP-Tagged Nanobodies Enable Reversible Optical Control of a G Protein-Coupled Receptor via a Remotely Tethered Photoswitchable Ligand

Kai Johnsson, Johannes Broichhagen, Helen Rebecca Ostlund Farrants

G protein-coupled receptors (GPCRs) mediate the transduction of extracellular signals into complex intracellular responses. Despite their ubiquitous roles in physiological processes and as drug targets for a wide range of disorders, the precise mechanisms ...

AMER CHEMICAL SOC2018

Potent Prearranged Positive Allosteric Modulators of the Glucagon-like Peptide-1 Receptor

Rosario Scopelliti, Johannes Broichhagen

Drugs that allosterically modulate G protein-coupled receptor (GPCR) activity display higher specificity and may improve disease treatment. However, the rational design of compounds that target the allosteric site is difficult, as conformations required fo ...

Wiley-V C H Verlag Gmbh2017

Computational Investigation of Intracellular Signalling Cascades : from G-Protein-Coupled Receptors to Adenylyl Cyclase

Siri Camee van Keulen

In order to adjust to changes in the environment, cells can communicate via signalling cascades. A common pathway for intercellular communication is the G-protein-coupled- receptor (GPCR) signal transduction cascade which is triggered by a (chemical or phy ...

EPFL2017

Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle

Caterina Collodet

AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic alpha-s ...

Amer Physiological Soc2016

Revealing GPCR oligomerization at the single-molecule level through a nanoscopic lens: methods, dynamics and biological function

Aleksandra Radenovic, Paolo Annibale, Marco Scarselli

The introduction of super-resolution fluorescence microscopy has allowed the visualization of single proteins in their biological environment. Recently, these techniques have been applied to determine the organization of class A G-protein-coupled receptors ...

Wiley-Blackwell2015

The Mechanism of Ligand-Induced Activation or Inhibition of - and -Opioid Receptors

Horst Arthur Vogel, Shuguang Yuan

G-protein-coupled receptors (GPCRs) are important targets for treating severe diseases. However why certain molecules act as activators whereas others, with similar structures, block GPCR activation, is poorly understood since the same molecule can activat ...

Wiley-Blackwell2015