The Mechanism of Ubiquitination in the Cullin-RING E3 Ligase Machinery: Conformational Control of Substrate Orientation
Figure 7
A scheme of the proposed pathway.
(A) Prior to binding to other E3 modules, the linker is flexible. (B) In the favored E3-bound conformation the substrate binding domain is rotated on the linker to the optimal position. (C) The strong correlations in the motions between the linker and the substrate binding domain in the bound state, suggest allosteric effects with the linker further rotating the substrate binding domain following substrate binding for optimal ubiquitin transfer position. (D) The linker rotates to facilitate additional ubiquitin transfer. (E) The linker rotation facilitates the poly-ubiquitin-labeled substrate dissociation from the E3 ligase.