Conformational sampling of CpxA: Connecting HAMP motions to the histidine kinase function

PLoS One Nathalie Duclert-Savatier, Guillaume Bouvier, Michael Nilges, Thérèse E. Malliavin

PLoS One. 2018; 13(11): e0207899. Published online 2018 Nov 29. doi: 10.1371/journal.pone.0207899

PMCID: PMC6264157 PMID: 30496238

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.