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Preferred Binding Mechanism of Osh4's Amphipathic Lipid-Packing Sensor Motif, Insights from Molecular Dynamics.
- Source :
-
The journal of physical chemistry. B [J Phys Chem B] 2018 Oct 25; Vol. 122 (42), pp. 9713-9723. Date of Electronic Publication: 2018 Oct 16. - Publication Year :
- 2018
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Abstract
- Amphipathic helices are key domains of peripheral membrane proteins, targeting specific membranes to enable proper protein function as well as changing the local topology and lipid dynamics of the membranes they bind. Here, we use extended all-atom molecular dynamics to study, in detail, the binding mechanism and conformation of the N-terminus of the lipid-transport protein Osh4 in yeast, that is, the amphipathic lipid-packing sensor (ALPS) motif. We identified two binding conformations: (i) a vertical one with the N-terminus of the peptide embedded into the hydrophobic core and (ii) a horizontal, and energetically favored, conformation in which the hydrophobic side chains of ALPS are fully embedded into the membrane hydrophobic core. From extensive analysis on 21 trajectories of 2 μs each, we describe peptide binding in terms of the structural changes that both the peptide and the membrane undergo upon binding as well as energetics of this interaction. The membrane models in this study include a simple binary lipid mixture, with a neutral and a charged lipid (1,2-dioleoyl- sn-glycero-3-phosphocholine-1,2-dioleoyl- sn-glycero-3-phospho-l-serine) and complex mixtures with lipid compositions characteristic of two organelles in yeast (each with more than six lipid types and an accurate sterol content). Our conclusions are in agreement with available literature, showing that the ALPS peptide is more likely to bind membrane surfaces with packing defects and higher anionic character. In addition, we show that there is an interplay between ALPS binding an existing packing defect and creating or enhancing one as the peptide binds to the membrane, which was previously suggested in the literature.
- Subjects :
- Amino Acid Motifs
Hydrophobic and Hydrophilic Interactions
Lipid Bilayers chemistry
Membrane Proteins chemistry
Molecular Dynamics Simulation
Peptide Fragments chemistry
Phosphatidylcholines chemistry
Phosphatidylcholines metabolism
Phosphatidylserines chemistry
Phosphatidylserines metabolism
Protein Binding
Protein Conformation
Receptors, Steroid chemistry
Saccharomyces cerevisiae chemistry
Saccharomyces cerevisiae Proteins chemistry
Thermodynamics
Lipid Bilayers metabolism
Membrane Proteins metabolism
Peptide Fragments metabolism
Receptors, Steroid metabolism
Saccharomyces cerevisiae Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5207
- Volume :
- 122
- Issue :
- 42
- Database :
- MEDLINE
- Journal :
- The journal of physical chemistry. B
- Publication Type :
- Academic Journal
- Accession number :
- 30281310
- Full Text :
- https://doi.org/10.1021/acs.jpcb.8b07067