Hydrophobic Mismatch Controls the Mode of Membrane-Mediated Interactions of Transmembrane Peptides

Abstract

Various cellular processes require the concerted cooperative action of proteins. The possibility for such synchronization implies the occurrence of specific long-range interactions between the involved protein participants. Bilayer lipid membranes can mediate protein–protein interactions via relatively long-range elastic deformations induced by the incorporated proteins. We considered the interactions between transmembrane peptides mediated by elastic deformations using the framework of the theory of elasticity of lipid membranes. An effective peptide shape was assumed to be cylindrical, hourglass-like, or barrel-like. The interaction potentials were obtained for membranes of different thicknesses and elastic rigidities. Cylindrically shaped peptides manifest almost neutral average interactions—they attract each other at short distances and repel at large ones, independently of membrane thickness or rigidity. The hourglass-like peptides repel each other in thin bilayers and strongly attract each other in thicker bilayers. On the contrary, the barrel-like peptides repel each other in thick bilayers and attract each other in thinner membranes. These results potentially provide possible mechanisms of control for the mode of protein–protein interactions in membrane domains with different bilayer thicknesses.

Simulation study of domain formation in a model bacterial membrane

“…Hydrophobic mismatch induced assembly of transmembrane peptides have been reported in the literature. 64–67…”

“…Hydrophobic mismatch induced assembly of transmembrane peptides have been reported in the literature. [64][65][66][67] To gain more insights into the structure and dynamics of the STX domains, we calculate mixing entropy and interfacial length of the membrane domains. Mixing entropy of the lipids are calculated using the formula…”

Construction of Saccharomyces cerevisiae KEX2-650 gene expression vector and its introduction into Escherichia coli DH5?

“…TMD has been known to influence the level of protein expression in all organisms, including yeast (Singh and Mittal 2016). It synchronizes with membrane protein or known as hydrophobic matching, which depends on the length of TMD and lipid bilayer thickness of the membrane protein (Kondrashov et al 2022). Therefore, TMD deletion has been known to increase the soluble recombinant protein level (Brenner and Fuller 1992).…”

Alteration of Average Thickness of Lipid Bilayer by Membrane-Deforming Inclusions

“…deform the membrane [20,21]. The lateral length of deformation decay in "conventional" membranes (e.g., formed from dioleoylphosphatidylcholine, DOPC) is of the order of several nanometers [21][22][23]. When the membrane-deforming objects are far-separated, their induced deformations are independent, and their energy is additive.…”