Fig. 3
From: Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm
Asymmetric binding of one ShhNp with two Ptch1. a Structural comparison of 2:1 Ptch1–ShhNp with our previously reported 1:1 Ptch1–ShhN complexes. The 2:1 Ptch1–ShhNp complex was ___domain colored. The 1:1 Ptch1–ShhN complex (PDB code 6DMY) was colored gray. The superimposition was made relative to Ptch1-G molecule. b The N-terminal peptide (N15) and palmitoyl moiety of ShhNp, which are well resolved in the 3.6 Å EM map for the 2:1 complex, interact extensively with ECD1 of Ptch1-P. The map, shown as blue mesh, was contoured at 6 σ. The potential electrostatic interactions are represented by dashed red lines. c The palmitate binding pocket in Ptch1-P. The hydrophobic residues in TMD-ECD connecting elements (including the Linker1, Neck helix 2, Linker7, and Neck helix 8) and hydrophobic surface residues in TM4/6/10/12 together constitute the binding pocket for the palmitate. The coordinating residues are shown as sticks and the palmitoyl moiety is shown as violet sphere. d The secondary interface between ShhNp and Ptch1-P. The globular ___domain of ShhNp interacts with ECD1 of Ptch1-P through limited polar interactions
