Extended Data Figure 8. A model for SL perception and signaling.

A model of the activity cycle underlying SL-induced and SCF D3-D14 mediated D53 poly-ubiquitination. D3 adopts two conformational states with a structurally variable C-terminal α-helix (left). With a dislodged CTH, D3 binds and inhibits D14 in its open conformation, until D53 is loaded (upper). D53 binding re-activates D14, which can hydrolyze SLs after or while D53 is poly-ubiquitinated. SL hydrolysis intermediate then stabilizes the closed conformation of D14, which converts D3-CTH into its engaged form. The resulting complex can ubiquitinate D14 and feed D3 back to the activity cycle (right). CLIM-bound D14 might participate in D53 poly-ubiquitination or in an alternative path (lower). It remains unknown how many SL molecules are hydrolyzed during the poly-ubiquitination of each D53 molecule.