Movie S1.

Interaction model of GC and LIMP-2 via two hydrophobic helical interfaces. Animation of crystal structures LIMP-2 (PDB ID code 4F7B) and GC (PDB ID code 2J25). The membrane-spanning LIMP-2 displays an exposed hydrophobic helical bundle (red). Its ligand, the lysosomal hydrolase GC, exhibits a similar hydrophobic motif (also shown in red). This binding model proposes interaction of LIMP-2/GC via these two helical interfaces (red). The amino acid sequence of the LIMP-2–derived helix 5 peptide, which was designed and used in this study, is highlighted in gold. We propose that the helix 5 peptide binds to the same hydrophobic interface on GC as shown for LIMP-2. Carbohydrate chains on both proteins are depicted in yellow.