Proposed locations of pore-lining side chains in TM1 and TM6. Location of residues that, when mutated to cysteine, are exposed to intracellular MTS reagents only (blue), to extracellular MTS reagents only (green), or to MTS reagents applied to either side of the membrane (red) (see also El Hiani and Linsdell, 2010). Other residues that we find not to be modified by intracellular MTS reagents and are presumed to be non–pore lining are shown in black. For TM1 (left), internal MTS modification is as shown in Fig. 2; external MTS modification is as defined in Fig. 4 or in previous work (Zhou et al., 2008). For TM6 (right), the model is as presented previously (El Hiani and Linsdell, 2010).