Structural characterization of protein interactions involved in type IV pili activation

To survive in their environments, interact with their host during infection and create complex communities, bacteria have evolved a wide range of sophisticated surface nanomachines (e.g flagella, secretion systems and surface pili). Among them, a family called Type-IV Pili (Tfp) is particularly widespread in bacteria and play key roles in adaptation, development and virulence. Although, it emerges that Tfps are highly conserved macromolecular structures, they have nevertheless evolved diverse cellular functions promoting adhesion to host cells, the import of extracellular DNA (competence), Kin recognition and cell motility (Twitching)1-3. Tfp machines assemble in the multilayered cell envelope and commonly work via the action of ATPases that extend/retract µm-long pilin filaments, which can attach to a large variety of surfaces and substrates1,2. In recent years, much progress have been made to determine the architecture of the two Tfp family member (Tfpa and Tfpb) at the molecular level4,5, especially with the first observation of the Tfpa basal body in Myxococcus xanthus by Cryo-electron tomography (cryo-ET)4. However, rather little is known on the mechanisms that activate Tfps function.
The PILACT project, funded by the French National Research Agency, aims to develop advanced multidisciplinary and collaborative approaches to unveil how a protein factor identified as essential for type IV pili activation connects to the Tfpa machinery to activate it and enable Twitching motility in the bacterium. This project proposes a global approach to study the molecular mechanisms involved in the activation of Twitching motility in the bacterium Myxococcus xanthus. It brings together two partners, Latifa Elantak (head of the "RMN des assemblages moléculaires" team at LISM) with expertise in nuclear magnetic resonance (NMR) studies of protein structures, dynamics and protein-protein interactions, and Tâm Mignot's team (Laboratoire de chimie bactérienne, Marseille) with expertise in cell biology, genetics and biochemistry on motility systems in the bacterium Myxococcus xanthus (ref. 1 & 2). The postdoctoral researcher recruited will contribute to the NMR structural characterization of the interactions involved.

References:
1-Bautista S, Schmidt V, Guiseppi A, Mauriello EMF, Attia B, Elantak L, Mignot T, Mercier R. FrzS acts as a polar beacon to recruit SgmX, a central activator of type IV pili during Myxococcus xanthus motility. EMBO J. 2023 Jan 4;42(1):e111661.
2-Mercier R, Bautista S, Delannoy M, Gibert M, Guiseppi A, Herrou J, Mauriello EMF, Mignot T. The polar Ras-like GTPase MglA activates type IV pilus via SgmX to enable twitching motility in Myxococcus xanthus. Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28366-28373.

The candidate will join the "NMR of molecular assemblies" team led by Latifa Elantak in the LISM Laboratory (CNRS UMR 7255). The team's research projects aim to understand the structural basis of protein assemblies that are functionally important for various aspects of the cell contacts with its microenvironment. Specifically, the candidate will work on the project concerning assemblies involved in the movement of bacteria on surfaces.
The anticipated start date is October/November 2023, with some flexibility as to the exact starting date.