The eukaryotic Elmo proteins (EnguLfment and cell MOtility) form a conserved regulatory family that plays a central role in a number of processes that depend on actin cytoskeleton remodeling, such as phagocytosis and cell migration. Elmo proteins regulate the function of Dock proteins (Downstream of CrK), a new family of atypical guanine exchange factors (GEF) for Rac1 and Cdc42 GTPases. The regulation of this mechanism is based on the interaction between the 200 C-terminal residues of Elmo and the 180 N-terminal residues of Dock. However, the precise role of the different domains and motifs identified in these regions is still not well defined. Indeed, functional, structural and biochemical data reported to date seem contradictory with respect to the contribution of the C-terminal end of Elmo, which includes a polyproline motif, and the N-terminal SH3 domain of Dock. We have therefore investigated the contribution of the C-terminal region of Elmo1 to the interaction between Elmo1 and the SH3 domain of Dock1 using surface plasmon resonance. Our data demonstrate the ability of the SH3 domain of Dock1 to interact with Elmo1 independently of the C-terminal polyproline containing region. However, the presence of this region induces a significant increase in the half-life of the Elmo1/Dock1 complex. In parallel, small angle X-ray experiments were recorded. These data allowed us to propose the first low-resolution model of Elmo1 in which we can locate N and C-terminal regions. Surprisingly, this study suggests a conformational change of the N-terminal region of Elmo1 and a possible interaction of this same region with the SH3 domain of Dock1
