Abstract
In the histidine kinase family, the HAMP and DHp domains are considered to play an important role into the transmission of signal arising from environmental conditions to the auto-phosphorylation site and to the binding site of response regulator. Several conformational motions inside HAMP have been proposed to transmit this signal: (i) the gearbox model, (ii) α helices rotations, pistons and scissoring, (iii) transition between ordered and disordered states. In the present work, we explore by temperature-accelerated molecular dynamics (TAMD), an enhanced sampling technique, the conformational space of the cytoplasmic region of histidine kinase CpxA. Several HAMP motions, corresponding to α helices rotations, pistoning and scissoring have been detected and correlated to the segmental motions of HAMP and DHp domains of CpxA.
Highlights
The two-component signaling systems (TCS) are ubiquitously used by prokaryotes to sense and respond to various changes in environmental conditions [1]
Collective variables have been chosen as geometric centers of Carbons α located in various protein regions: HAMP and DHp α helices and catalytic and ATP-binding (CA) domains
The geometric centers of HAMP α helices are generic collective variables not related to specific relative motions of the helices, the use of such collective variables permitted to observe relative motions of the helices, similar to the motions observed along a metadynamics analysis of an isolated HAMP domain [41]
Summary
The two-component signaling systems (TCS) are ubiquitously used by prokaryotes to sense and respond to various changes in environmental conditions [1]. TCS control a large diversity of cellular functions in bacteria [2,3,4,5,6,7,8] and can regulate virulence and pathogenicity [9,10,11,12,13]. A two-component system is composed of two proteins, a sensor histidine kinase (HK) and a response regulator (RR) [14]. Histidine kinases are multifunctional enzymes that share a conserved intracellular catalytic core linked to highly diverse signal sensors. The large majority of histidine kinases, the so-called class I HKs [15], are homo-dimeric membrane proteins in which the cytoplasmic region contains two distinct functional domains: an N-terminal dimerization and histidine
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