Both piston-like and rotational motions are present in bacterial chemoreceptor signaling.

Daqi Yu,Xiaomin Ma,Yuhai Tu,Luhua Lai

doi:10.1038/srep08640

Abstract

Bacterial chemotaxis signaling is triggered by binding of chemo-effectors to the membrane-bound chemoreceptor dimers. Though much is known about the structure of the chemoreceptors, details of the receptor dynamics and their effects on signaling are still unclear. Here, by using molecular dynamics simulations and principle component analysis, we study the dynamics of the periplasmic domain of aspartate chemoreceptor Tar dimer and its conformational changes when binding to different ligands (attractant, antagonist, and two attractant molecules). We found two dominant components (modes) in the receptor dynamics: a relative rotation of the two Tar monomers and a piston-like up-and-down sliding movement of the α4 helix. These two modes are highly correlated. Binding of one attractant molecule to the Tar dimer induced both significant piston-like downward movements of the α4 helix and strong relative rotations of the two Tar monomers, while binding of an antagonist or the symmetric binding of two attractant molecules to a Tar dimer suppresses both modes. The anti-symmetric effects of the relative rotation mode also explained the negative cooperativity between the two binding pockets. Our results suggest a mechanism of coupled rotation and piston-like motion for bacterial chemoreceptor signaling.

Highlights

Bacterial chemotaxis signaling is triggered by binding of chemo-effectors to the membrane-bound chemoreceptor dimers
Recent Molecular dynamics (MD) simulations[19] showed that restrained piston-like downward sliding of the a4 helix in the periplasmic domain can propagate the signal by affecting the transmembrane and the HAMP domains of the receptor
In this paper, we studied five different systems: 1) the apo system (E. coli Tar periplasmic domain, with residues 36–181) without any ligand, 2) Tar dimer binding with one Asp, 3) Tar dimer binding with one CHDCA, 4) Tar dimer binding with one cis-PDA, 5) Tar dimer binding with two Asps

Summary

Introduction

Bacterial chemotaxis signaling is triggered by binding of chemo-effectors to the membrane-bound chemoreceptor dimers. We found two dominant components (modes) in the receptor dynamics: a relative rotation of the two Tar monomers and a piston-like up-and-down sliding movement of the a4 helix. By comparing the crystal structures, it has been proposed that the transmembrane signaling was triggered by a relative piston-like downward sliding of the a4 helix in the periplasmic domain after attractant binding[1,12,13,14]. Aside from the novel attractant molecules, such as, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, guanidinosuccinic acid, we found two antagonists, cis-1, 2-cyclohexane-dicarboxylic acid (CHDCA) and phthalic acid (PA), which directly bind to Tar without causing any chemotactic responses. Given that attractants and antagonists of Tar bind to the same binding pocket as the cognate attractant (Asp), it raises the interesting question of how they induce different chemotactic responses

Methods

Results

Conclusion