Fig. 2: Binding and interaction details of (-)ML-SI3 and (+)ML-SI3.

a Structural comparison between ML-SI3–bound TRPML1 (7MGL) in gray and (-)ML-SI3–bound TRPML2 in green with the compounds shown in their respective colors. b Zoom-in comparison of molecule orientation between the two compounds in a, with the π-bulge indicated. c Interaction details of (-)ML-SI3–bound TRPML2 with important residues shown as sticks. Residues in gray denote a neighboring subunit. d Comparison of apo (yellow), and (+)ML-SI3–bound pre-open (light blue) TRPML2 with the α-helix indicated, and the movement of the S4-S5 linker denoted by a red arrow. e Interaction details of (+)ML-SI3–bound pre-open TRPML2 with residues shown as sticks and (+)ML-SI3 shown in purple. Residues in gray denote a neighboring subunit. f Comparison of apo (yellow), and (+)ML-SI3–bound open (blue) TRPML2 with the π-bulge indicated, and the movement of the S4-S5 linker denoted by a red arrow. g Interaction details of (+)ML-SI3–bound open TRPML2 with residues shown as sticks and (+)ML-SI3 shown in dark blue. Residues in gray denote a neighboring subunit. h Comparison of the poses of ML-SI3 in three structures and Y496 labeled as sticks.