Figure 4. Uncoating of CCVs by Hsc70.

A) Structure of clathrin heavy chain/auxilin basket (PDB 1XI5). The smallest unit from which a basket can be generated by symmetry operations is shown, centered on a vertex with the clathrin terminal domain (TD; aa 1–331) in green, the linker and ankle (aa 331–800) in cyan, the distal leg (800–1200) in purple, the proximal leg (aa 1200–1597) in blue and the tripod (aa 1598–1630) in rose. The auxilin J domain is in yellow. Suppression of mutants of auxilin D876 (in red) by mutations of Hsc70 R172 indicates that these two residues approach each other in the complex, allowing Hsc70 (shown with the SBD in red and the NBD in magenta) to be modeled onto the auxilin. B) The structure from A, rotated as indicated so that the view is from the interior of the basket and centered on a vertex. The TD, auxilin and tripod are labeled. One Hsc70 molecule is modeled (‘1’), and two others would occupy the threefold related positions in the ellipses labeled ‘2’ and ‘3’. Elements of the heavy chain legs lie interposed between the tripod and the Hsc70s. C) Expanded view of the boxed region from A, with the Hsc70 removed, but its position indicated by an ellipse. Also suggested is how the extended C-terminal tail (in pink) could emerge from the portal formed by the ankle and distal legs to be bound by the Hsc70 molecule. D) Schematic of the organization of the uncoating machinery: Hsc70 may bind the C-terminal tail in a manner analogous to an unfolded polypeptide emerging from an import pore.