title: Structure of the human ADP-ribosylation factor 1 complexed with GDP.
abstract: ADP-ribosylation factors (ARFs) are essential and ubiquitous in eukaryotes, being involved in vesicular transport and functioning as an activator of phospholipase D (refs 1, 2) and cholera toxin. The functions of ARF proteins in membrane traffic and organelle integrity are intimately tied to its reversible association with membranes and specific interactions with membrane phospholipids. One common feature of these functions is their regulation by the binding and hydrolysis of GTP. Here we report the three-dimensional structure of full-length human ARF1 (M(r) 21,000) in its GDP-bound non-myristoylated form. The presence of a unique amino-terminal alpha-helix and loop, together with differences in Mg2+ ligation and the existence of a non-crystallographic dimer, set this structure apart from other GTP-binding proteins. These features provide a structural basis for the GTP-dependent modulation of membrane affinity, the lack of intrinsic GTPase activity, and the nature of effector binding surfaces.
authors.affiliation: Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.
authors.forename: J C
authors.initials: JC
authors.lastname: Amor
authors.forename: D H
authors.initials: DH
authors.lastname: Harrison
authors.forename: R A
authors.initials: RA
authors.lastname: Kahn
authors.forename: D
authors.initials: D
authors.lastname: Ringe
mesh_terms: D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000737:chemistry; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D019204:GTP-Binding Proteins; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; D008274:Magnesium