Figure 3

Possible structural basis for phospholipid scrambling by BR. (a) Space-fill representation of BR structure (from PDBID: 4MD2), showing positively charged residues (blue), negatively charged residues (red) and polar residues (green). The potential lipid-translocation path is shown within the dotted lines. (b) Cartoon model of BR (PDBID: 4MD2) using the same color code as for panel a, specifying the polar amino acid residues that are proposed to form the lipid translocation pathway. (c,d) Structure of a trimer of BR viewed from the exoplasmic side (c) and from the membrane (d), generated by the PDBePISA algorithm from PDBID: 4MD2. The residues that are proposed to be involved in the lipid translocation pathway are represented in space fill (and labeled in panel d) and lipid molecules from the structure are drawn in white. The individual BR monomers in the trimer are shown in trace representation and are colored differently – orange, cyan and green; for clarity only 2 protomers of the trimer are depicted in panel d. (e,f) Top (e) and side (f) views of BR (illustrated in trace representation of its backbone) from the CGMD simulations showing accumulation of water molecules near TMs 1 and 2. Different protomers of the trimer are colored as in panels c,d, with relevant residues shown in space fill representation and labeled in panel f. Red spheres represent superposition from all the trajectory frames of Martini water beads (1 bead equivalent to 4 water molecules) within 7 Å of residues T17, G21, T24, and T47. In panel f, only 2 protomers of the trimer are depicted for clarity. Note the involvement of Y147 from the TM5 helix of the adjacent protomer in solvation of the interfacial region.