Publications related to New designs for submillimetric press-fitting

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

Screening for drivers of SARS-CoV-2 uptake

Christoph Merten, Alexis Louis Autour

Genetic and cellular drivers of the cellular uptake of SARS-CoV-2 can be screened at high throughput via droplet microfluidics and size-exclusion methods for the analysis of the formation of fusions between cells expressing the virus's spike protein and ce ...

Nature Portfolio2023

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

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

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

Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist

Henning Paul-Julius Stahlberg, Nicolas Calo, Polina Isaikina

The human CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) that plays a major role in inflammation and is involved in cancer, HIV, and COVID-19. Despite its importance as a drug target, the molecular activation mechanism of CCR5, i.e., ...

AMER ASSOC ADVANCEMENT SCIENCE2021

Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state

Anne-Marinette Thi Phuong Hanh Cao

Here, the authors use smFRET to assess the structural dynamics of metabotropic glutamate receptor mGlu2 and show that a positive allosteric modulator or the Gi protein stabilize mGlu2 in the glutamate-induced active state, leading to the full activation of ...

Nature Portfolio2021

Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers

Horst Vogel, Shuguang Yuan

Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop receptor family are key players in fast signal transduction throughout the nervous system. They have been shown to be modulated by the lipid environment, however the underlying mechanism is not ...

Nature Research2021

Enhancing the Signaling of GPCRs via Orthosteric Ions

Horst Vogel, Shuguang Yuan

G protein-coupled receptors play essential roles in cellular processes such as neuronal signaling, vision, olfaction, tasting, and metabolism. As GPCRs are the most important drug targets, understanding their interactions with ligands is of utmost importan ...

AMER CHEMICAL SOC2020

Ligand Binding to the Collagen VI Receptor Triggers a Talin-to-RhoA Switch that Regulates Receptor Endocytosis

Béatrice Kunz, Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami, Matteo Dal Peraro, Shixu Yan, Luciano Andres Abriata

Capillary morphogenesis gene 2 (CMG2/ANTXR2) is a cell surface receptor for both collagen VI and anthrax toxin. Biallelic loss-of-function mutations in CMG2 lead to a severe condition, hyaline fibromatosis syndrome (HFS). We have here dissected a network o ...

Cell Press - Elsevier2020

MMP9/RAGE pathway overactivation mediates redox dysregulation and neuroinflammation, leading to inhibitory/excitatory imbalance: a reverse translation study in schizophrenia patients

Lijing Xin, Basilio Giangreco, Daniella Dwir, Kim Do

ious mechanisms involved in schizophrenia pathophysiology, such as dopamine dysregulation, glutamate/NMDA receptor dysfunction, neuroinflammation or redox imbalance, all appear to converge towards an oxidative stress "hub" affecting parvalbumine interneuro ...

2020

Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster

Bruno Lemaitre, Andrew Jonathan Bretscher, Jan Paul Dudzic, Elodie Julie Virginie Ramond, Claudia Melcarne

Eater and NimC1 are transmembrane receptors of the Drosophila Nimrod family, specifically expressed in haemocytes, the insect blood cells. Previous ex vivo and in vivoRNAi studies have pointed to their role in the phagocytosis of bacteria. Here, we have cr ...

2019

The endosomal sorting adaptor HD-PTP is required for ephrin-B: EphB signalling in cellular collapse and spinal motor axon guidance

Daniel Eduardo Morales Garza

The signalling output of many transmembrane receptors that mediate cell-cell communication is restricted by the endosomal sorting complex required for transport (ESCRT), but the impact of this machinery on Eph tyrosine kinase receptor function is unknown. ...

Nature Research2019

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

Kai Johnsson, Helen Rebecca Ostlund Farrants, Johannes Broichhagen

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

Dual optical control and mechanistic insights into photoswitchable group II and III metabotropic glutamate receptors

Johannes Broichhagen

G protein-coupled receptor (GPCR) signaling occurs in complex spatiotemporal patterns that are difficult to probe using standard pharmacological and genetic approaches. A powerful approach for dissecting GPCRs is to use light-controlled pharmacological age ...

National Academy of Sciences2017

Physiological regulation of the CDK16/PCTAIRE-1 protein kinase and its proposed role in the brain

Saifeldin Nasser Mohamed Ibrahim Shehata

Cell signalling, mediated to a large extent by protein kinase phosphorylation, plays a vital role in regulation of cellular function. PCTAIRE-1 (also known as cyclin-dependent protein kinase (CDK)16), is a Ser/Thr kinase that has been implicated in many ce ...

EPFL2017

Stress, glucocorticoid receptor and social behaviors

Peripuberty, comprising childhood and adolescence, constitutes an important time window in the brain development and maturation. Exposure to prolonged stress during this period has been shown to increase the risk for the development of psychopathologies la ...

EPFL2017

Single-molecule microscopy to study plasma membrane receptor dynamics

Luc Veya

Cell surface receptors allowthe cell to sense and respond to external signals. Receptor malfunctions are associated with many diseases. The diffusional behavior of receptors is of particular interest to understand how the cell modulates receptor function i ...

EPFL2016

Subunit-selective N-Methyl-D-aspartate (NMDA) Receptor Signaling through Brefeldin A-resistant Arf Guanine Nucleotide Exchange Factors BRAG1 and BRAG2 during Synapse Maturation

Michael Kintscher

The maturation of glutamatergic synapses in the CNS is regulated by NMDA receptors (NMDARs) that gradually change from a GluN2B- to a GluN2A-dominated subunit composition during postnatal development. Here we show that NMDARs control the activity of the sm ...

Amer Soc Biochemistry Molecular Biology Inc2016