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Lipid-mediated interactions tune the association of glycophorin A helix and its disruptive mutants in membranes
- Source :
- Physical Chemistry Chemical Physics, 12(40), 12987-12996. ROYAL SOC CHEMISTRY
- Publication Year :
- 2010
-
Abstract
- The specific and non-specific driving forces of helix association within membranes are still poorly understood. Here, we use coarse-grain molecular dynamics simulations to study the association behavior of glycophorin A and two disruptive mutants, T87F and a triple mutant of the GxxxG motif (G79LG83LG86L), embedded in a lipid membrane. Self-assembly simulations and the association free-energy profile confirm an energetically-favorable dimerized state for both the wild type and the mutants. The reduced association of the mutants compared to the wild type, as observed in experiments, can be justified from comparisons of the free energy profiles. Less-favorable protein-protein interactions as well as disruption of lipid packing around the mutant dimers is responsible for their reduced association. The role of the non-specific "lipid-phobic'' contribution appears to be as important as the specific "helix-helix'' contribution. However, the differences between the wild type and mutants are subtle and our simulations predict a dimerization state not only for the wild-type glycophorin A, but also for these 'disruptive' mutants. Our results highlight the importance of both specific as well as non-specific driving forces in the association of transmembrane helices, and point to the need of more careful interpretation of experimental measurements.
- Subjects :
- MOLECULAR-DYNAMICS SIMULATIONS
Amino Acid Motifs
Mutant
General Physics and Astronomy
Plasma protein binding
Molecular Dynamics Simulation
Protein Structure, Secondary
Protein structure
Glycophorin
Glycophorins
Physical and Theoretical Chemistry
Lipid bilayer
DIMERIZATION MOTIF
DIMER
biology
Chemistry
Cell Membrane
Wild type
Biological membrane
PROTEIN STRUCTURE
FREE-ENERGY
Lipids
SELF-ASSOCIATION
Transmembrane domain
HYDROPHOBIC MISMATCH
Amino Acid Substitution
Biochemistry
Mutation
Biophysics
biology.protein
FORCE-FIELD
Dimerization
TRANSMEMBRANE ALPHA-HELICES
Protein Binding
BIOLOGICAL MEMBRANE
Subjects
Details
- Language :
- English
- ISSN :
- 14639076
- Volume :
- 12
- Issue :
- 40
- Database :
- OpenAIRE
- Journal :
- Physical Chemistry Chemical Physics
- Accession number :
- edsair.doi.dedup.....05c1fbbee55bfc29e44e59d784049f80