Structural insights into the small GTPase specificity of the DOCK guanine nucleotide exchange factors

The dedicator of cytokinesis (DOCK) family of guanine nucle-otide exchange factors (GEFs) regulates cytoskeletal dy-namics by activating the GTPases Rac and/or Cdc42. Eleven human DOCK proteins play various important roles in devel-opmental processes and the immune system. Of these, DOCK1-5 proteins bind to engulfment and cell motility (ELMO) proteins to perform their physiological functions. Recent structural studies have greatly enhanced our under-standing of the complex and diverse mechanisms of DOCK GEF activity and GTPase recognition and its regulation by ELMO. This review is focused on gaining structural insights into the substrate specificity of the DOCK GEFs, and discuss how Rac and Cdc42 are specifically recognized by the catalytic DHR-2 and surrounding domains of DOCK or binding partners.