Work

Protein-induced membrane asymmetry modulates OMP folding kinetics and stability

Year: 2025

Type: article

Abstract: . Here, we present a method exploiting the efficient, unidirectional folding of the transmembrane β-barrel outer membrane protein, OmpA, to create asymmetric proteoliposomes with protein-induced dipoles of known direction (arising from sequence variation engineered into the OmpA loops). We then characterise the folding kinetics and stability of different OmpA variants into these proteoliposomes. We find that both the primary sequence of the folding OmpA and the dipole of the membrane into which folding occurs play an important role for modulating the rate of folding. Critically, we find that by complementarily matching the charge on the folding protein to the membrane dipole it is possible to enhance both the folding kinetics and the stability of the folded OmpA. The results hint at how cells might exploit loop charge in membrane-embedded proteins to manipulate membrane environments for adaptation and survival.

Source: Faraday Discussions

DOI: 10.1039/d4fd00180j

Authors: Jonathan M. Machin, Neil A. Ranson, Sheena E. Radford

Institution: University of Leeds

Language: English

Topic: Lipid Membrane Structure and Behavior

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funders: Wellcome Trust, Royal Society, Medical Research Council

Awards: Breaking the Barrier: Mapping protein interactions in the bacterial outer membrane as targets for new antimicrobials, Structure, dynamics and function of OMPs in physiological-like membranes, G804879125