Assembly of the Transmembrane Domain of E. coli PhoQ Histidine Kinase: Implications for Signal Transduction from Molecular Simulations

作者：Lemmin Thomas^*; Soto Cinque S; Clinthorne Graham; DeGrado William F; Dal Peraro Matteo

来源：PLoS Computational Biology, 2013, 9(1): e1002878.

DOI：10.1371/journal.pcbi.1002878

The PhoQP two-component system is a signaling complex essential for bacterial virulence and cationic antimicrobial peptide resistance. PhoQ is the histidine kinase chemoreceptor of this tandem machine and assembles in a homodimer conformation spanning the bacterial inner membrane. Currently, a full understanding of the PhoQ signal transduction is hindered by the lack of a complete atomistic structure. In this study, an atomistic model of the key transmembrane (TM) domain is assembled by using molecular simulations, guided by experimental cross-linking data. The formation of a polar pocket involving Asn202 in the lumen of the tetrameric TM bundle is crucial for the assembly and solvation of the domain. Moreover, a concerted displacement of the TM helices at the periplasmic side is found to modulate a rotation at the cytoplasmic end, supporting the transduction of the chemical signal through a combination of scissoring and rotational movement of the TM helices.

• 出版日期2013-1