Interhelical h-bonds modulate the activity of a polytopic transmembrane kinase

RUYSSCHAERT, JEAN MARIE; CYBULSKI, LARISA ESTEFANÍA; BORTOLOTTI, ANA; INDA, MARÍA EUGENIA; ALMADA, JUAN CRUZ; DE MENDOZA, DIEGO

Biomolecules

MDPI AG

Lugar: Basel; Año: 2021 vol. 11 p. 1 - 12

DesK is a Histidine Kinase that allows Bacillus subtilis to maintain lipid homeostasis in response to changes in the environment. It is located in the membrane, and has five transmembrane helices and a cytoplasmic catalytic domain. The transmembrane region triggers the phosphorylation of the catalytic domain as soon as the membrane lipids rigidify. In this research, we study how transmembrane inter-helical interactions contribute to signal transmission; we designed a coexpression system that allows studying in vivo interactions between transmembrane helices. By Alanine-replacements, we identified a group of polar uncharged residues, whose side chains contain hydrogen-bond donors or acceptors, which are required for the interaction with other DesK transmembrane helices; a particular array of H-bond-residues plays a key role in signaling, transmitting information detected at the membrane level into the cell to finally trigger an adaptive response.