Fig. 8: Structure of FAM92A1 BAR domain and molecular simulation of FAM92A1 membrane remodeling mechanism. | Nature Communications

Fig. 8: Structure of FAM92A1 BAR domain and molecular simulation of FAM92A1 membrane remodeling mechanism.

From: Membrane remodeling by FAM92A1 during brain development regulates neuronal morphology, synaptic function, and cognition

Fig. 8

a Crystal structure of human FAM92A1 BAR domain (residues 1–219). The three α-helices in chain B were labeled with α1, α2, and α3. NT, N-terminus, CT, C-terminus. b The electrostatic potential surface of FAM92A1 BAR domain. The membrane interacting concave surface is indicated with a curve line, box with dashed lines encloses the central 6-helix bundle of the dimer. c The structure of FAM92A1 BAR homodimer interface. Hydrophobic residues and polar residues involved in hydrogen-bonded interactions are shown in green and cyan, respectively. d Superimposition of the FAM92A1 BAR domain with the existing structures of the BAR domain subfamilies. e The hypothesized oligomerization mode and interface at the distal arm tips of two adjacent FAM92A1 dimers, interface indicated with a black sphere. f Normalized occupancy of FAM92A1 amino acid residues with membrane phospholipids. g 2D density plots showing the distribution of lipids around the FAM92A1 BAR domain monomer. The values have been averaged over the last 100 ns and across the replicate simulations. h Schematic representation of FAM92A1 BAR domain dimer on MIM, PI(4,5)P2, and cardiolipin bilayer, respectively, at the beginning (start time, t = 0) and end (t = 1 µs) of the simulation. The phospholipid head groups are shown as teal spheres. POPC, cyan; POPE, gray; POPS, pink; PI(4,5)P2, blue; cardiolipin, magenta. i Line plot showing the evolution of FAM92A1 BAR domain dimer concave conformation during the simulation period. Inset, residues constituting the angle chosen to estimate the change in FAM92A1 BAR domain dimer concave conformation. j Line plot showing the curvature profile of membrane leaflet with (upper) or without (lower) FAM92A1 bound. The position of phosphate atoms of the membrane phospholipids has been binned at intervals of 1 nm along the long axis (x-axis) of the membrane. For (i) and (j) data represent mean ± SD of three biologically independent simulations. Source data provided as a Source Data file.

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