Structure of the guanine nucleotide exchange factor Sec7 domain of human arno and analysis of the interaction with ARF GTPase

Cell. 1998 Feb 6;92(3):415-23. doi: 10.1016/s0092-8674(00)80933-2.


Sec7-related guanine nucleotide exchange factors (GEFs) initiate vesicle budding from the Golgi membrane surface by converting the GTPase ARF to a GTP-bound, membrane-associated form. Here we report the crystal structure of the catalytic Sec7 homology domain of Arno, a human GEF for ARF1, determined at 2.2 angstroms resolution. The Sec7 domain is an elongated, all-helical protein with a distinctive hydrophobic groove that is phylogenetically conserved. Structure-based mutagenesis identifies the groove and an adjacent conserved loop as the ARF-interacting surface. The sites of Sec7 domain interaction on ARF1 have subsequently been mapped, by protein footprinting experiments, to the switch 1 and switch 2 GTPase regions, leading to a model for the interaction between ARF GTPases and Sec7 domain exchange factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 1
  • ADP-Ribosylation Factors
  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry*
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins*
  • Guanine Nucleotide Exchange Factors*
  • Guanosine Diphosphate / metabolism
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary*
  • Sequence Analysis
  • Sequence Deletion
  • Sequence Homology, Amino Acid


  • Fungal Proteins
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Sec7 guanine nucleotide exchange factors
  • cytohesin-2
  • Guanosine Diphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • ADP-Ribosylation Factor 1
  • ADP-Ribosylation Factors