Phd Postdoc Day - 2021 July 5th

The first CBS PhD/postdoc meeting will be held on Monday, the 5th of July via Zoom ! This day will gather all non-permanent young researchers from the CBS, allowing them to meet, present their work and talk with each other about raised topics. Moreover, two special guests will be invited to present their careers. Since they were two former students from the CBS and borrowed two different paths in the research world, meeting them will permit to highlight any specificities according to both academic and private careers.




Cryo-EM structure of the V2R:AVP:Gs complex


The cryo-EM structure of the antidiuretic hormone arginine-vasopressin V2 receptor signaling complex


Arginine-vasopressin (AVP) is known as the antidiuretic hormone, and it regulates a vital function of our body, water homeostasis. It plays a role in the kidney at the basolateral membranes of the principal cells of the distal collecting duct of the nephron where it directly interacts with the V2 receptor subtype (V2R), which is a typical G protein-coupled receptor (RCPGs). Upon interaction, AVP activates a signaling pathway leading to fusion of aquaporine water channels to the apical membrane of the cells and consequently to water reabsorption from urine to blood. Coupling of the V2R to the Gs protein constitutes a first key step of the cellular response.

The Team « Multi-scale structural biology » in collaboration with the Team of Bernard Mouillac and Sébastien Granier from the IGF (Montpellier), determined the structure of the AVP-V2R-Gs ternary complex by cryo-electron microscopy single particle analysis in combining the cryo-EM density map with experimental NMR (Nuclear Magnetic Resonance) data obtained by Hélène Déméné (Team « Integrative Biophysics of Membranes », CBS) and computational molecular dynamic simulations developed by Nicolas Floquet at the Institut des Biomolécules Max Mousseron (IBMM).

This study reveals the extremely strong dynamics of the AVP-V2R-Gs ternary complex since three conformational states were observed reflecting different modes of interaction of AVP and the Gs protein. These structures make it possible to understand how certain mutations induce two genetics, congenital nephrogenic diabetes insipidus and the nephrogenic syndrome of inappropriate antidiuresis.

This study paves the way to the development of new therapeutic molecules able to activate or to inhibit its function. This research perspective is crucial regarding patients who are suffering for these pathologies which are difficult to manage.

Link to the article :

Cryo-electron microscopy structure of the antidiuretic hormone arginine-vasopressin V2 receptor signaling complex.
J. Bous, H. Orcel, N. Floquet, C. Leyrat, J. Lai-Kee-Him, G. Gaibelet, A. Ancelin, J. Saint-Paul, S. Trapani, M. Louet, R. Sounier, H. Déméné, S. Granier*, P. Bron*, B. Mouillac*. Science Advances, 7, eabg5628 (2021).


Dynamic stiffening of the flagellar hook

For many bacteria, motility stems from one or more flagella, each rotated by the bacterial flagellar motor, a powerful rotary molecular machine. The hook, a soft polymer at the base of each flagellum, acts as a universal joint, coupling rotation between the rigid membrane-spanning rotor and rigid flagellum. In multi-flagellated species, where thrust arises from a hydrodynamically coordinated flagellar bundle, hook flexibility is crucial, as flagella rotate significantly off-axis. However, consequently, the thrust applies a significant bending moment. Therefore, the hook must simultaneously be compliant to enable bundle formation yet rigid to withstand large hydrodynamical forces. Here, via high-resolution measurements and analysis of hook fluctuations under dynamical conditions, we elucidate how it fulfills this double functionality: the hook shows a dynamic increase in bending stiffness under increasing torsional stress. Such strain-stiffening allows the system to be flexible when needed yet reduce deformation under high loads, enabling high speed motility.

Full text:

Pedaci Nature

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Applications for Master are open until June 6th, 2022

The C-terminal domains of GPCR are disordered with transient secondary structures

Arrestin-dependent pathways are a central component of G protein-coupled receptor (GPCR) signaling. This pathway is activated after the phosphorylation of the GPCR C-terminal domain, which allows the recruitment of arrestin. However, the molecular processes regulating arrestin binding is not yet well understood due to the lake of structural information of the C-terminal disordered regions. Here we used an integrated biophysical strategy to describe globally and at atomic scale the basal conformations of the C-terminal domains of three class A GPCRs, the vasopressin receptor (V2R), the ghrelin receptor (GHSR) and the b2-Adernergic Receptor (b2AR). Our work revealed the presence of transient secondary structures in these regions that are potentially involved in the interaction with arrestin. These secondary structure elements differ from those described in the literature in interaction with arrestin. This suggests a mechanism where the secondary structure conformational preferences in the C-terminal regions of GPCRs could be a central feature for optimizing arrestins recognition.

Myriam Guillien, Assia Mouhand, Aurélie Fournet, Amandine Gontier, Aleix Martí Navia, Tiago N. Cordeiro, Frédéric Allemand, Aurélien Thureau, Jean-Louis Banères, Pau Bernadó and Nathalie Sibille*

Full Text:

 Cter GPCR