Fig. 9: Schematic of conformational changes of DOCK2–ELMO1 and membrane attachment model.
From: Structure of the DOCK2−ELMO1 complex provides insights into regulation of the auto-inhibited state
a In the DOCK2–ELMO1–RAC1 ternary complex, ELMO1NTD adopts the open conformation with binding sites for RAC1, RHOG and BAI1 exposed on DOCK2DHR2, ELMO1RBD and ELMO1EID (on ELMO1NTD), respectively. In the closed, auto-inhibited state of the DOCK2–ELMO1 binary complex (the dominate state for DOCK2–ELMO1), rotation of ELMO1NTD by 120° about an elbow hinge connecting ELMO1NTD with ELMO1PH causes ELMO1NTD to form contacts with DOCK2DHR2 and ELMO1PH. These new interfaces create an auto-inhibited state that occludes binding sites for RAC1, RHOG and BAI. Phosphorylation of ELMO1 on either the phosphorylation linker (Fig. 1c) or Tyr 18 of ELMO1RBD (Fig. 4d) would disrupt the closed state. The view is similar to Figs. 3a, b and 6d. b Membrane attachment sites for DOCK2 and RAC1 are situated on the same face of the DOCK2−ELMO1−RAC1 complex. PIP3 binds to a site defined by the L1 loop of DOCK2DHR1 incorporating Lys437, Lys440 and Lys444, whereas RAC1 attaches to the membrane through a prenyl group attached to Cys189. Leu177 denotes the last ordered residue of the RAC1 crystal structure.
