Publications by Bruno Claude Daniel Fauvet

Hsp110 Nucleotide Exchange Factors may amplify Hsp70-disaggregation by enhanced entropic pulling

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Mathieu Rebeaud

Hsp70s use energy from ATP hydrolysis to unfold protein structures and solubilize stable aggregates and accumulate native species, even under adverse non-native conditions. To carry out its catalytic polypeptide-unfolding activity, Hsp70 needs to reversibl ...

Elsevier BV2025

Autorepression of yeast Hsp70 cochaperones by intramolecular interactions involving their J-domains

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Adélaïde Alice Mohr, Satyam Tiwari, Mathieu Rebeaud, Pierre Goloubinoff

The 70 kDa heat shock protein (Hsp70) chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) coevolved with Hsp70s to trigger ATP hydrolysis and catalytically upload various substrate polypeptides in ne ...

Elsevier Science Inc2024

A fluorescent multi-domain protein reveals the unfolding mechanism of Hsp70

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Salvatore Assenza, Satyam Tiwari, Pierre Goloubinoff

Detailed understanding of the mechanism by which Hsp70 chaperones protect cells against protein aggregation is hampered by the lack of a comprehensive characterization of the aggregates, which are typically heterogeneous. Here we designed a reporter chaper ...

NATURE PORTFOLIO2022

Repair or Degrade: the Thermodynamic Dilemma of Cellular Protein Quality-Control

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Satyam Tiwari, Mathieu Rebeaud, Pierre Goloubinoff

Life is a non-equilibrium phenomenon. Owing to their high free energy content, the macromolecules of life tend to spontaneously react with ambient oxygen and water and turn into more stable inorganic molecules. A similar thermodynamic picture applies to th ...

FRONTIERS MEDIA SA2021

Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Alessandro Barducci, Alberto Stefano Sassi, Pierre Goloubinoff

During and after protein translation, molecular chaperones require ATP hydrolysis to favor the native folding of their substrates and, under stress, to avoid aggregation and revert misfolding. Why do some chaperones need ATP, and what are the consequences ...

2018

Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding

Juan Kiwi, Bruno Claude Daniel Fauvet, Hilal Lashuel, Anass Chiki, Farah El Turk

Intracellular deposits of α-synuclein in the form of Lewy bodies are major hallmarks of Parkinson’s disease (PD) and a range of related neurodegenerative disorders. Post-translational modifications (PTMs) of α-synuclein are increasingly thought to be major ...

2018

Molecular chaperones inject energy from ATP hydrolysis into the non-equilibrium stabilisation of native proteins

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Alessandro Barducci, Alberto Stefano Sassi, Pierre Goloubinoff

Protein homeostasis, namely the ensemble of cellular mechanisms collectively controlling the activity, stability and conformational states of proteins, depends on energy-consuming processes. De novo protein synthesis requires ATP hydrolysis for peptide bon ...

2017

Membrane scission driven by the PROPPIN Atg18

Bruno Claude Daniel Fauvet, Hilal Lashuel, Andreas Mayer

Sorting, transport, and autophagic degradation of proteins in endosomes and lysosomes, as well as the division of these organelles, depend on scission of membrane-bound tubulo-vesicular carriers. How scission occurs is poorly understood, but family protein ...

Nature Publishing Group2017

The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease

Bruno Claude Daniel Fauvet, Hilal Lashuel, Magdalena Zweckstetter, Sebastian Kugler

Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with age-associated neurodegenerative disorders such as Alzheimer and Parkinson disease ( ...

2017

Semisynthetic and in Vitro Phosphorylation of Alpha-Synuclein at Y39 Promotes Functional Partly Helical Membrane-Bound States Resembling Those Induced by PD Mutations

Bruno Claude Daniel Fauvet, Hilal Lashuel, Farah El Turk, Ana Jovicic, Carole Desobry, Anne-Laure Mahul Mellier

Alpha-synuclein is a presynaptic protein of poorly understood function that is linked to both genetic and sporadic forms of Parkinson's disease. We have proposed that alpha-synuclein may function specifically at synaptic vesicles docked at the plasma membr ...

Amer Chemical Soc2016

The H50Q Mutation Enhances alpha-Synuclein Aggregation, Secretion, and Toxicity

Giovanni Dietler, Bruno Claude Daniel Fauvet, Hilal Lashuel, Martial Mbefo Kamdem, Abid Oueslati, Filip Vercruysse, Francesco Simone Ruggeri, Ossama Mohamed Salah El-Dien El-Sayed Ibrahim Khalaf, Anne-Laure Mahul Mellier

Over the last two decades, the identification of missense mutations in the alpha-synuclein (alpha-Syn) gene SNCA in families with inherited Parkinson disease (PD) has reinforced the central role of alpha-Syn in PD pathogenesis. Recently, a new missense mut ...

American Society for Biochemistry and Molecular Biology2014

Protein semisynthesis and total synthesis approaches to elucidate the role of Alpha-Synuclein post-translational modifications

Bruno Claude Daniel Fauvet

EPFL2014

Alpha-synuclein Post-translational Modifications as Potential Biomarkers for Parkinson Disease and Other Synucleinopathies

Bruno Claude Daniel Fauvet, Hilal Lashuel, Adrian Schmid, Marc Moniatte

The development of novel therapies against neurodegenerative disorders requires the ability to detect their early, presymptomatic manifestations in order to enable treatment before irreversible cellular damage occurs. Precocious signs indicative of neurode ...

Amer Soc Biochemistry Molecular Biology Inc2013

Characterization of semisynthetic and naturally Nα-acetylated α-synuclein in vitro and in intact cells: implications for aggregation and cellular properties of α-synuclein

Bruno Claude Daniel Fauvet, Hilal Lashuel, Mohamed Bilal Fares

N-terminal acetylation is a very common post-translational modification, although its role in regulating protein physical properties and function remains poorly understood. α-Synuclein (α-syn), a protein that has been linked to the pathogenesis of Parkinso ...

Amer Soc Biochemistry Molecular Biology Inc2012

Characterization of Molecular Determinants of the Conformational Stability of Macrophage Migration Inhibitory Factor: Leucine 46 Hydrophobic Pocket

Ursula Röthlisberger, Bruno Claude Daniel Fauvet, Hilal Lashuel, Hajer Ouertatani-Sakouhi, Michele Cascella, Farah El Turk, Marilisa Neri, Florence Pojer, Amer Ashrafi, Min Kyu Cho, Magdalena Zweckstetter

Macrophage Migration Inhibitory Factor (MIF) is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer f ...

Public Library of Science2012

Chemical strategies for controlling protein folding and elucidating the molecular mechanisms of amyloid formation and toxicity

Loay Awad, Bruno Claude Daniel Fauvet, Hilal Lashuel, Mirva Hejjaoui

It has been more than a century since the first evidence linking the process of amyloid formation to the pathogenesis of Alzheimer's disease. During the last three decades in particular, increasing evidence from various sources (pathology, genetics, cell c ...

Elsevier2012

Elucidating the role of C-terminal post-translational modifications using protein semisynthesis strategies: α-synuclein phosphorylation at tyrosine 125

Michel Prudent, Bruno Claude Daniel Fauvet, Hilal Lashuel, Mirva Hejjaoui, Filip Vercruysse, Yao Zhang

Despite increasing evidence that supports the role of different post-translational modifications (PTMs) in modulating α-synuclein (α-syn) aggregation and toxicity, relatively little is known about the functional consequences of each modification and whethe ...

2012

Phosphorylation of alpha-Synuclein at Y125 and S129 Alters Its Metal Binding Properties: Implications for Understanding the Role of alpha-Synuclein in the Pathogenesis of Parkinson's Disease and Related Disorders

Hubert Girault, Michel Prudent, Bruno Claude Daniel Fauvet, Hilal Lashuel, Yu Lu

alpha-Synuclein (alpha-syn) is a 140-amino acid protein that plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. However, the molecular determinants that are responsible for triggering and/or propagating alpha- ...

American Chemical Society2011

Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action

Bruno Claude Daniel Fauvet, Hilal Lashuel, Hajer Ouertatani-Sakouhi, Farah El Turk, Min Kyu Cho, Magdalena Zweckstetter

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is considered an attractive therapeutic target in multiple inflammatory and autoimmune disorders. In addition to its known biologic activities, MIF can also function as a tautomerase ...

American Society for Biochemistry and Molecular Biology2010

An integrative in silico methodology for the identification of modulators of macrophage migration inhibitory factor (MIF) tautomerase activity

Bruno Claude Daniel Fauvet, Hilal Lashuel, Hajer Ouertatani-Sakouhi, Farah El Turk

Macrophage migration inhibitory factor (MIF) is a major proinflammatory cytokine that has been increasingly implicated in the pathogenesis of several inflammatory, autoimmune, infectious and oncogenic diseases. Accumulating evidence suggests that the tauto ...

Elsevier2010