title: Elliptical structure of phospholipid bilayer nanodiscs encapsulated by scaffold proteins: casting the roles of the lipids and the protein.
abstract: Phospholipid bilayers host and support the function of membrane proteins and may be stabilized in disc-like nanostructures, allowing for unprecedented solution studies of the assembly, structure, and function of membrane proteins (Bayburt et al. Nano Lett. 2002, 2, 853-856). Based on small-angle neutron scattering in combination with variable-temperature studies of synchrotron small-angle X-ray scattering on nanodiscs in solution, we show that the fundamental nanodisc unit, consisting of a lipid bilayer surrounded by amphiphilic scaffold proteins, possesses intrinsically an elliptical shape. The temperature dependence of the curvature of the nanodiscs prepared with two different phospholipid types (DLPC and POPC) shows that it is the scaffold protein that determines the overall elliptical shape and that the nanodiscs become more circular with increasing temperature. Our data also show that the hydrophobic bilayer thickness is, to a large extent, dictated by the scaffolding protein and adjusted to minimize the hydrophobic mismatch between protein and phospholipid. Our conclusions result from a new comprehensive and molecular-based model of the nanodisc structure and the use of this to analyze the experimental scattering profile from nanodiscs. The model paves the way for future detailed structural studies of functional membrane proteins encapsulated in nanodiscs.
authors.affiliation: Biophysics, Faculty of Life Sciences, University of Copenhagen, DK-1165 Copenhagen, Denmark.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Skar-Gislinge
authors.forename: Jens Bæk
authors.initials: JB
authors.lastname: Simonsen
authors.forename: Kell
authors.initials: K
authors.lastname: Mortensen
authors.forename: Robert
authors.initials: R
authors.lastname: Feidenhans'l
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Sligar
authors.forename: Birger
authors.initials: B
authors.lastname: Lindberg Møller
authors.forename: Thomas
authors.initials: T
authors.lastname: Bjørnholm
authors.forename: Lise
authors.initials: L
authors.lastname: Arleth
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008962:Models, Theoretical; D049329:Nanostructures / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D010743:Phospholipids