Structure of the GAT domain of human GGA1: a syntaxin amino-terminal domain fold in an endosomal trafficking adaptor.

Abstract

The Golgi-associated, gamma-adaptin homologous, ADP-ribosylation factor (ARF)-interacting proteins (GGAs) are adaptors that sort receptors from the trans-Golgi network into the endosomallysosomal pathway. The GGAs and TOM1 (GAT) domains of the GGAs are responsible for their ARF-dependent localization. The 2.4-A crystal structure of the GAT domain of human GGA1 reveals a three-helix bundle, with a long N-terminal helical extension that is not conserved in GAT domains that do not bind ARF. The ARF binding site is located in the N-terminal extension and is separate from the core three-helix bundle. An unanticipated structural similarity to the N-terminal domain of syntaxin 1a was discovered, comprising the entire three-helix bundle. A conserved binding site on helices 2 and 3 of the GAT domain three-helix bundle is predicted to interact with coiled-coil-containing proteins. We propose that the GAT domain is descended from the same ancestor as the syntaxin 1a N-terminal domain, and that both protein families share a common function in binding coiled-coil domain proteins.