Panel A: A horizontal dot plot shows the positions of charged residues within TMDs of single-pass proteins. The plot is divided into three regions: exoplasmic interfacial region (top 20 percent, light gray shading), hydrophobic core (central 60 percent, beige shading), and cytosolic interfacial region (bottom 20 percent, light gray shading). Each dot represents a single charged residue (R, dark blue; K, light blue; E, dark red; D, light red) plotted at its relative depth within a schematic membrane cross-section. Positive: negative charge ratios and overall charge densities are shown for each region on the right. Panel B: A similar horizontal dot plot shows the positions of charged residues within TMDs of an n-matched random subsample of multi-pass TMDs. The layout and color coding are the same as in Panel A. Panel C: Two bar graphs display the distributions of net exoplasmic (top) and cytosolic (bottom) flanking charges for single-pass (blue) and multi-pass (red) TMDs. The horizontal axis represents the net charge, and the vertical axis represents the proportion of TMDs. Panel D: Two bar graphs show the distributions of net exoplasmic (top) and cytosolic (bottom) flanking charges for signal anchor TMDs (SA, yellow) and downstream TMDs (green). The horizontal axis represents the net charge, and the vertical axis represents the proportion of TMDs.
Distribution of charged residues within and flanking TMDs. (A and B) Dot plots showing the positions of all charged residues within TMDs of single-pass proteins (A) and an n-matched random subsample of multipass TMDs (B). Each dot represents a single charged residue (R, dark blue; K, light blue; E, dark red; D, light red) plotted at its relative depth within a schematic membrane cross-section. The membrane is divided into an exoplasmic interfacial region (top 20%, light gray shading), hydrophobic core (central 60%, beige shading), and cytosolic interfacial region (bottom 20%, light gray shading), Positive:negative charge ratios and overall charge densities (i.e., percent aa that are charged) are shown for each region on the right. (C) Distributions of net exoplasmic (top) and cytosolic (bottom) flanking charges (the sum of charged residues in the interfacial region of the TMD plus the 10 flanking residues on each side) for single-pass (blue) and multipass (red) TMDs. (D) As in C, but for SA TMDs (first TMD of proteins lacking a cleavable signal; yellow) and downstream TMDs (all subsequent TMDs in multipass proteins; green).