Mechanism of transmembrane signaling by sensor histidine kinases

Ivan Yu. Gushchin (1, 2, 3) , Igor I Melkinov (4) , Vitaly Polovinkin (1, 3, 2) , Andrii Ishchenko (5, 6, 2) , Anastasia Yuzhakova (1, 2) , Pavel Buslaev (1) , Gleb Bourenkov (6) , Sergei Grudinin (7, 1) , Ekaterina Round (3, 2) , Taras Balandin (2) , Valentin Borshchevskiy (1, 2) , Dieter Willbold (2, 8) , Gordon Leonard (4) , Georg Büldt (1) , Alexander Popov (4) , Valentin I. Gordeliy (1, 3, 2)

1 MIPT - Moscow Institute of Physics and Technology [Moscow]
2 ICS - Institute of Complex Systems
3 IBS - UMR 5075 - Institut de biologie structurale
4 ESRF - European Synchrotron Radiation Facility
5 Institute of Crystallography [Aachen]
6 EMBL - European Molecular Biology Laboratory [Hamburg]
7 NANO-D - Algorithms for Modeling and Simulation of Nanosystems
8 Institut für Physikalische Biologie [Düsseldorfd]

One of the major and essential classes of transmembrane (TM) receptors, present in all domains of life, is sensor histidine kinases (HKs), parts of two-component signaling systems (TCS). The structural mechanisms of transmembrane signaling by these sensors are poorly understood. We present here crystal structures of the periplasmic sensor domain, the TM domain and the cytoplasmic HAMP domain of the Escherichia coli nitrate/nitrite sensor HK NarQ in the ligand-bound and mutated ligand-free states. The structures reveal that the ligand binding induces significant rearrangements and piston-like shifts of TM helices. The HAMP domain protomers undergo lever-like motions and convert the piston-like motions into helical rotations. Our findings provide the structural framework for complete understanding of TM TCS signaling and for development of antimicrobial treatments targeting TCS.

Mots clés: Protein structure; Protein crystallography

Domaines: Biologie structurale [q-bio.BM]; Biophysique [physics.bio-ph]; Modélisation et simulation

Ivan Yu. Gushchin, Igor I Melkinov, Vitaly Polovinkin, Andrii Ishchenko, Anastasia Yuzhakova, et al.. Mechanism of transmembrane signaling by sensor histidine kinases. Science, 2017, 356 (6342), pp.eaah6345. ⟨10.1126/science.aah6345⟩. ⟨hal-01526454⟩