title: 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.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: Silke
authors.initials: S
authors.lastname: Suer
authors.forename: Saurav
authors.initials: S
authors.lastname: Misra
authors.forename: Layla F
authors.initials: LF
authors.lastname: Saidi
authors.forename: James H
authors.initials: JH
authors.lastname: Hurley
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D050827:Syntaxin 1
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000954:Antigens, Surface; D002352:Carrier Proteins; C407306:GGA adaptor proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C494212:STX1A protein, human; D050827:Syntaxin 1; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors