Interhelical H-Bonds Modulate the Activity of a Polytopic Transmembrane Kinase

• Main Authors: Juan Cruz Almada, Ana Bortolotti, Jean Marie Ruysschaert, Diego de Mendoza, María Eugenia Inda, Larisa Estefanía Cybulski
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Biomolecules
• Subjects: transmembrane protein interactions; hydrogen bond interaction; signal transduction; histidine kinase; dimerisation motif; receptor
• Online Access: https://www.mdpi.com/2218-273X/11/7/938

DesK is a Histidine Kinase that allows <i>Bacillus subtilis</i> 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 co-expression 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.