Fig. 3

Structural alignment by TM-align of CAVER-identified transporter tunnels in SLC25 family members predicted to be associated with glutathione metabolic processes. a Heatmap of TM-scores for pairwise alignments of tunnel-interacting regions identified by CAVER for candidate SLC25 members. Values are TM-scores normalized to the sequence length of the column protein. b & c Visualization of pairwise transporter tunnel alignments for SLC25A39 (dark purple) and most similar SLC25 candidates by TM-score, SLC25A43 (green) and SLC25A24 (orange). Indicated residues are those identified as relevant for GSH transport by SLC25A39 and corresponding residues in SLC25A43 and SLC25A24. Protein tunnels visualized from the intermembrane space with tunnel-interacting residues identified by CAVER highlighted and non-tunnel residues faded. d–f In silico binding of GSH by known and predicted mGSH transporters. GSH-bound SLC25A39 (purple) is aligned to GSH-bound structures of SLC25A43 (orange), SLC25A24 (green), and SLC25A10 (blue). GSH structures are coloured according to their bound protein structure