title: Self-assembling peptides form nanodiscs that stabilize membrane proteins.
abstract: New methods to handle membrane bound proteins, e.g. G-protein coupled receptors (GPCRs), are highly desirable. Recently, apoliprotein A1 (ApoA1) based lipoprotein particles have emerged as a new platform for studying membrane proteins, and it has been shown that they can self-assemble in combination with phospholipids to form discoidal shaped particles that can stabilize membrane proteins. In the present study, we have investigated an ApoA1 mimetic peptide with respect to its solution structure when in complex with phospholipids. This was achieved using a powerful combination of small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) supported by coarse-grained molecular dynamics simulations. The detailed structure of the discs was determined in unprecedented detail and it was found that they adopt a discoidal structure very similar to the ApoA1 based nanodiscs. We furthermore show that, like the ApoA1 and derived nanodiscs, these peptide discs can accommodate and stabilize a membrane protein. Finally, we exploit their dynamic properties and show that the 18A discs may be used for transferring membrane proteins and associated phospholipids directly and gently into phospholipid nanodiscs.
authors.affiliation: Department of Chemistry, University of Copenhagen, Denmark. kjj@chem.ku.dk.
authors.forename: Søren Roi
authors.initials: SR
authors.lastname: Midtgaard
authors.forename: Martin Cramer
authors.initials: MC
authors.lastname: Pedersen
authors.forename: Jacob Judas Kain
authors.initials: JJ
authors.lastname: Kirkensgaard
authors.forename: Kasper Kildegaard
authors.initials: KK
authors.lastname: Sørensen
authors.forename: Kell
authors.initials: K
authors.lastname: Mortensen
authors.forename: Knud J
authors.initials: KJ
authors.lastname: Jensen
authors.forename: Lise
authors.initials: L
authors.lastname: Arleth
mesh_terms: D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D045333:Nanotubes, Peptide / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D055550:Protein Stability
chemical_list: D016632:Apolipoprotein A-I; D008565:Membrane Proteins; D045333:Nanotubes, Peptide; D010455:Peptides; D010743:Phospholipids