Molecular model of a sensor of two-component signaling system

Yury L Ryzhykau,Georg Büldt,Mikhail Yu Nikolaev,Dmytro Volkov ,Dmitrii Zabelskii ,Martin Engelhard,A.v Vlasov ,Gordon A Leonard ,Martha Brennich ,I A Melnikov ,Maksim Rulev ,T N Murugova ,Ivan Gushchin ,Dmitri I Svergun,Montserrat Soler-López ,Philipp Orekhov ,Andrey Gruzinov ,Vladimir Chupin ,Andrey Rogachev ,Arne Bothe,Alexander I Kuklin

doi:10.1038/s41598-021-89613-6

Abstract

Two-component systems (TCS) are widespread signaling systems present in all domains of life. TCS typically consist of a signal receptor/transducer and a response regulator. The receptors (histidine kinases, chemoreceptors and photoreceptors) are often embedded in the membrane and have a similar modular structure. Chemoreceptors were shown to function in highly ordered arrays, with trimers of dimers being the smallest functional unit. However, much less is known about photoreceptors. Here, we use small-angle scattering (SAS) to show that detergent-solubilized sensory rhodopsin II in complex with its cognate transducer forms dimers at low salt concentration, which associate into trimers of dimers at higher buffer molarities. We then fit an atomistic model of the whole complex into the SAS data. The obtained results suggest that the trimer of dimers is "tripod"-shaped and that the contacts between the dimers occur only through their cytoplasmic regions, whereas the transmembrane regions remain unconnected.

Highlights

Two-component systems (TCS) are widespread signaling systems present in all domains of life
The combination of small-angle scattering (SAS) and molecular modeling has allowed us to propose a molecular model of the full-length phototaxis complex from the halophilic archaeon N. pharaonis and to reveal the effect of salt concentration on its oligomeric state and dynamics
The monomer–monomer interactions between transducers are in accordance with the following high-resolution structural data

Summary

Introduction

Two-component systems (TCS) are widespread signaling systems present in all domains of life. A recent work indicated that TCS networks expressed in mammalian cells might pave the way for orthogonal s ignaling[2] This will require more atomic level detail concerning their structure/function relationships. In this regard, detailed information has been obtained for chemotaxis and photoreceptor TCS of motile enteric bacteria and archaea, respectively[3,4]. This family of TCS consist of a transmembrane receptor, which interacts with a His-kinase (CheA) and adaptor proteins (CheW) attached at their cytoplasmic tips. The sensor domain constitutes a microbial rhodopsin which forms a 2:2 complex with its cognate transducer (Htr). Together with CheA and CheW, trimers form the core unit of the extended signaling a rrays[14], compact membrane-attached assemblages of signaling units responsible for amplification of the incoming s timulus[15,16,17]

Methods

Findings

Conclusion