QscR Homologues

By comparing QscR with homologous LuxR-family proteins such as TraR and CviR, we see how structural similarity between QscR and its homologues can reflect specialised functions and regulatory mechanisms of each individual quorum sensing signal receptor.

TraM as an antiactivator to TraR

TraM (monomer MW 11.4kD) has been identified as the antiactivator to TraR (monomer MW 27kD) in the formation of inhibition oligomeric complex (115kD) with two TraM homodimers binding between the LBD and DBD of two TraR homodimers symmetrically. TraM disrupts the TraR-DNA complex and further prevents free TraR from binding DNA. Qin et al (2007) shows that the formation of the 2TraM₂-2TraR₂ species involves a two-step process as described below (also see Fig 1):

Fig 1: (A) Two-step processes of 115kD 2TraM2-2TraR2 species formation.
(B) Crystal structure showing 77kD TraR2-TraM2-dsDNA complex. Each colour represents an individual TraR or TraM monomer. DNA double helix is in yellow.
Source: Qin et al, 2007

1. DBD of a TraR protomer  (a structural subunit of an oligomer) binds to the tra box DNA. Due to the asymmetric configuration of DNA-bound TraR dimer, N-terminal overhang of the other protomer blocks C-terminal TraM binding site of the first, so only one TraM dimer binds to the TraR-DNA complex forming the stable 77kD TraM₂-TraR₂-dsDNA complex.
2. Upon DNA release from the complex, the previously occluded TraM binding site is now exposed and readily interacts with another TraM dimer which may be bound to a TraR dimer, forming the 115kD 2TraM₂-2TraR₂ species where the TraM dimers lock the TraR DBDs into a rigid conformation, therefore unable to bind DNA.

On an interesting note, another protein QslA has been shown to demonstrate similar antiactivator function in QslA-LasR interaction. Seet and Zhang (2011) noted that QslA seems to be involved in setting the threshold level of Quorum Sensing signal required to trigger subsequent response. In the absence of QslA, P. aeruginosa requires only one-ninth (1/9) of the AHL concentration (3OC12-HSL) to stimulate Quorum Sensing activation compared to wild-type. However, the molecular details of such mechanisms are yet unknown.

CviR and antagonism

When CviR is bound to its antagonist the DBDs change conformation and interact with LBDs. This keeps the two DBDs away from one another and they are prevented from binding DNA. The protein's cross-subunit architecture allows rapid switch of the receptor from the inactive to the active state. 

The active state is presented well by QscR which adopts the ideal configuration for DNA binding. On the other hand, CviR can be used to represent the inactive receptor conformation. For a receptor to switch to the active state i.e. CviR to QscR conformation, the DBDs just need to swing around. However we still do not know if this configuration persists when the receptor is bound on the DNA.

LuxR family receptors may have similar architecture but they exist in great structural diversity. This makes it difficult for scientists to obtain a general mechanism for their function, therefore further structural studies are essential to fully understand the nuts and bolts of the intricate machinery.

Fig 2: CviR structure bound to antagonist. DBDs are shown in red. At a distance  of 60A away from each other, it is impossible to bind DNA. Ideal distance for activation is about 30A. [Source: Chen G. et al, 2011]