Dock180 - Structure and Function

Structure and Function

Dock180 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting this nucleotide exchange.

Dock180 and related proteins differ from other GEFs in that they do not possess the canonical structure of tandem DH-PH domains known to elicit nucleotide exchange. Instead they possess a DHR2 domain which mediates Rac activation by stabilising it in its nucleotide-free state. Dock180-related proteins also possess a DHR1 domain which has been shown, in vitro, to bind phospholipids and which may be involved in their interaction with cellular membranes. Other structural features of Dock180 include an N-terminal SH3 domain involved in binding to ELMO proteins (see below) and a C-terminal proline-rich region which, in Myoblast city (the Drosophila melanogaster ortholog of Dock180), was shown to bind DCrk (the Drosophila ortholog of Crk).