a, The chemical structure of cotransin CP2 and the positions of amino acids (ovals) of Sec61 in the immediate vicinity are drawn in a two-dimensional representation. Different colors were used for ovals to indicate regions in Sec61α: purple–plug, brown–pore ring, gray–lateral gate, light and dark oranges–polar cluster Q127/N300, and white–others. In the cotransin CP2 chemical structure, main lipid-exposed parts are in green whereas channel-facing parts are in blue. Moieties in orange and red interact with N300 and Q127 respectively. b–g, As in a, but drawn for decatransin (b), apratoxin F (c), mycolactone (d), ipomoeassin F (e), CADA (f), and ESI (g). Dashed lines indicate putative hydrogen bonds. Note that in the mycolactone-bound structure, a water molecule coordinated by Sec61 and mycolactone was observed in the pocket. For 3D structures, see Extended Data Fig. 8.