FrzS acts as a polar beacon to recruit SgmX, a central activator of type IV pili during Myxococcus xanthus motility

Abstract

In rod-shaped bacteria, type IV pili (Tfp) promote twitching motility by assembling and retracting at the cell pole. In Myxococcus xanthus, a bacterium that moves in highly coordinated cell groups, Tfp are activated by a polar activator protein, SgmX. However, while it is known that the Ras-like protein MglA is required for unipolar targeting, how SgmX accesses the cell pole to activate Tfp is unknown. Here, we demonstrate that a polar beacon protein, FrzS, recruits SgmX at the cell pole. We identified two main functional domains, including a Tfp-activating domain and a polarbinding domain. Within the latter, we show that the direct binding of MglA-GTP unveils a hidden motif that binds directly to the FrzS N-terminal response regulator (CheY). Structural analyses reveal that this binding occurs through a novel binding interface for response regulator domains. In conclusion, the findings unveil the protein interaction network leading to the spatial activation of Tfp at the cell pole. This tripartite system is at the root of complex collective behaviours in this predatory bacterium.

Unorthodox regulation of the MglA Ras‐like GTPase controlling polarity in Myxococcus xanthus

“…The localization mechanism is now well understood: The SgmX C-terminal domain, consisting of three tetratricopeptide repeat (TPR) domaina well-known protein-protein interaction, structural motif -, forms an MglA-GTP-binding domain, which when binding unfolds an otherwise hidden secondary binding site to the polar landmark protein FrzS [52]. This allows recruitment of SgmX to the cell pole where it activates the TFP machinery via its N-terminal activation domain [52]. The exact activation mechanism is still under study and could be linked to dynamic interactions between SgmX and the PilB pilus extension motor [37,38].…”

“…(A) Collective motility (referred to as Social‐motility) involves Type‐IV pili that undertake cycles of extension and retraction at the leading pole to pull the cell forward. MglA complexed to GTP interacts and recruits the newly identified TFP regulator protein SgmX, therefore unmasking the FrzS‐binding domain of SgmX to activate S‐motility machinery at the bacterial cell pole [52]. The different domains of SgmX are represented as follows: blue is the Tfpa‐activating domain, black tail represents the C‐terminal domain and the dark‐orange and yellow circles represent the TPR domain.…”

Distinct dynamics and proximity networks of hub proteins at the prey-invading cell pole in a predatory bacterium

“…We, therefore, propose to rename Bd2492 as SgmX1 and Bd2490 as SgmX2. Both proteins only align with the N-terminal part of M. xanthus SgmX involved in Type IV pili activation in M. xanthus (44), but not with the C-terminal part required for MglA interaction (45). Their potential role in pili activation in B. bacteriovorus and their interaction with MglA remains to be experimentally tested in B. bacteriovorus .…”

RomX, a novel prokaryotic regulator, links the response receiver domain of RomR with GTP-bound MglA for establishingMyxococcus xanthuspolarity

“…When the bound GTP is hydrolyzed, the protein in the GDP-bound state detaches from the pole and diffuses in the cytoplasm. In the active GTP bound state, it interacts with SgmX, an effector, and also plays a role in the correct polar localization of PilB and PilT ATPases, all of which are critical to S-motility [22][23][24] . It also interacts with AglZ in the GTP state, localizing to the focal adhesion complex-like gliding motors, and manifesting the cell movement 15,[25][26][27][28] .…”