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Reprogramming G Protein-Coupled Receptor Structure, Function And Signaling By Computational Design
Related publications (123)
Computationally designed GPCR quaternary structures bias signaling pathway activation
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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 ...
2022Rational design of protein switches: applications in synthetic biology and cancer immunotherapy
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 ...
EPFL2022Hitting the Bullseye: Endogenous Electrophiles Show Remarkable Nuance in Signaling Regulation
Yimon Aye, Pierre Alexander Miranda Herrera
ABSTRACT: 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 electrophile ...
AMER CHEMICAL SOC2022Computationally 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 now be readily characterized, receptor associati ...
2021Computational design of highly signaling active membrane receptors through de novo solvent-mediated allosteric networks
Jian Wang, Patrick Daniel Barth
Protein catalysis and allostery require the atomic-level orchestration and motion of residues, ligand, solvent and protein effector molecules, but the ability to design protein activity through precise protein-solvent cooperative interactions has not been ...
2021Structural 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 SCIENCE2021Allosteric 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 PORTFOLIO2021Gαi1 inhibition mechanism of ATP-bound adenylyl cyclase type 5
Ursula Röthlisberger, Siri Camee van Keulen, Daniele Narzi
Conversion of adenosine triphosphate (ATP) to the second messenger cyclic adenosine monophosphate (cAMP) is an essential reaction mechanism that takes place in eukaryotes, triggering a variety of signal transduction pathways. ATP conversion is catalyzed by ...
2021The role of metal ions in G protein-coupled receptor signalling and drug discovery
Horst Vogel, Shuguang Yuan, Xueying Wang
Metal ions, such as Na+, Mg2+, Ca2+, and Zn2+, are highly abundant in biological systems. For many G protein-coupled receptors (GPCRs), metal ions, especially Na+, have been found to stabilize the receptors' inactivate state preventing receptor activation. ...
WILEY2021Evolutionary history expands the range of signaling interactions in hybrid multikinase networks
Anne-Florence Raphaëlle Bitbol, Mohamed Barakat
Two-component systems (TCSs) are ubiquitous signaling pathways, typically comprising a sensory histidine kinase (HK) and a response regulator, which communicate via intermolecular kinase-to-receiver domain phosphotransfer. Hybrid HKs constitute non-canonic ...
NATURE RESEARCH2021