Extended Data Fig. 7: Lipid interaction in a high-resolution structure of TTYH2. | Nature

Extended Data Fig. 7: Lipid interaction in a high-resolution structure of TTYH2.

From: Interactions between TTYH2 and APOE facilitate endosomal lipid transfer

Extended Data Fig. 7: Lipid interaction in a high-resolution structure of TTYH2.

a, TTYH2 particles not containing density corresponding to APOE were selected from the dataset of TTYH2 in complex with delipidated APOE and the three datasets of TTYH2 in complex with coexpressed APOE. The resulting particle set was used for ab initio reconstruction and 3D refinement yielding a map at 2.7 Å resolution. b, Fourier shell correlation (FSC) plot of the final refined cryo-EM density map of the TTYH2 structure at 2.7 Å with pronounced density of bound lipids. c, Density of TTYH2 viewed along the long dimensions of the dimeric molecule (colored in cyan and magenta) with lipid density colored in yellow. d, Lipid interaction region in the TTYH2 dimer viewed from opposite sides. The protein is shown as ribbon (colored in cyan and magenta), refined positions of lipid and cholesterol molecules as sticks. 15 well defined lipids and 6 cholesterol molecules are colored in yellow, 5 putative lipids with weaker density in brown. Lipids are labeled corresponding to their interacting subunit and shown as blow-up with their respective cryo-EM density superimposed (map contour: 2’, 6 σ; 3’, 5.5 σ; 1, 1’, 2, 3, 5, 6’, 12’, 5 σ; 6, 7’, 9, 10’, 11, 11’, 13, 14, 4.5 σ; 4’, 5’, 7, 8’, 9’, 4.0 σ; 4, 8, 10, 3.5 σ; 12, 3.5 σ). e, Region surrounding the N-terminal helix N1 peripherally attached to the membrane and, f, region surrounding the hydrophobic cavity emerging from the membrane with interacting lipids (colors and numbering is as defined in d). The molecular surface is shown in white.

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