Fig. 4.
Unpredicted packing arrangements and burial of the SOCS2 N and C termini. (A) The side chain of V198 at the C terminus packs into a deep pocket in the back of the SH2 domain, and the terminal carboxyl forms hydrogen bond interactions with W48 (SH2) and Y194 (SOCS box). This conformation is stabilized by R168, which is strictly conserved within the SOCS family but not within the VHL BC box or Skp2 F box. (B) The ESS forms a single amphipathic helix (blue) that packs between the SH2 (orange) and SOCS box (red) domains with hydrophobic and electrostatic interactions, respectively, that bury a surface area of ≈1,200 Å2.