title: Mechanistic explanation of different unfolding behaviors observed for transmembrane and soluble β-barrel proteins.
abstract: In response to mechanical stress, membrane proteins progress through sequences of major unfolding barriers, whereas soluble proteins usually must overcome only one major unfolding barrier. To gain insight into these markedly different unfolding behaviors, we applied force-probe molecular dynamics simulations and unfolded two β-barrel proteins, the transmembrane outer membrane protein G (OmpG) and the water-soluble green fluorescent protein (GFP). The simulations mimic with high precision the unfolding experiments and show that OmpG in the absence of a membrane and GFP circumvent high unfolding barriers by rotations and explore alternative unfolding pathways. Embedding OmpG in the lipid membrane restricts this search for pathways and forces the protein to cross high unfolding barriers. Likewise, restricting the rotation forces GFP to traverse high unfolding barriers in a similar manner to membrane-embedded OmpG. These results indicate that mechanically stressed proteins search alternative unfolding pathways by rotations and explain why membrane proteins generally show higher mechanical stability compared to water-soluble proteins.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel CH-4058, Switzerland.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hensen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D037402:Hydrozoa; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D018272:Porins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding; D013816:Thermodynamics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D008051:Lipid Bilayers; C114347:OmpG protein, E coli; D018272:Porins; C485192:green fluorescent protein, Aequorea victoria; D049452:Green Fluorescent Proteins