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Structure of the Sec7 domain of the Arf exchange factor ARNO

Nature volume 392, pages 101–105 (1998)Cite this article

Abstract

Small G proteins switch from a resting, GDP-bound state to an active, GTP-bound state. As spontaneous GDP release is slow, guanine-nucleotide-exchange factors (GEFs) are required to promote fast activation of small G proteins through replacement of GDP with GTP in vivo1. Families of GEFs with no sequence similarity to other GEF families have now been assigned to most families of small G proteins. In the case of the small G protein Arf1, the exchange of bound GDP for GTP promotes the coating of secretory vesicles in Golgi traffic2. An exchange factor for human Arf1, ARNO3, and two closely related proteins, named cytohesin 1 (ref. 4) and GPS1 (ref. 5), have been identified. These three proteins are modular proteins with an amino-terminal coiled-coil, a central Sec7-like domain and a carboxy-terminal pleckstrin homology domain. The Sec7 domain contains the exchange-factor activity3. It was first found in Sec7, a yeast protein involved in secretion6, and is present in several other proteins, including the yeast exchange factors for Arf, Gea1 and Gea2 (7–9). Here we report the crystal structure of the Sec7 domain of human ARNO at 2 Å resolution and the identification of the site of interaction of ARNO with Arf.

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Figure 1: Structure of ARNO-Sec7.
Figure 2: Topography of the conserved motives of ARNO-Sec7.
Figure 3: The putative site of binding to Arf.
Figure 4: Nucleotide-exchange activity of ARNO-Sec7 mutants on Arf1.

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Acknowledgements

We thank the staff at the LURE for making outstation W32 available to us; M. Roth at the ESRF for beamlight assistance at outstation D2AM; S. Bryant and T. Madej for the Protein Data Bank survey with VAST; J.-F. Gibrat for sequence-threading calculations; S. Paris for unpublished observations; and M. Chabre and J. Janin for discussions. This work was supported by the Association pour la Recherche contre le Cancer and by Zénéca Pharma (France). M.M. was supported by an EMBO fellowship.

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  1. Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR 9063, Gif-sur-Yvette, 91198, France

    Jacqueline Cherfils, Julie Ménétrey, Magali Mathieu & Gérard Le Bras

  2. Institut de Pharmacologie Moléculaire et Cellulaire du CNRS-UPR 411, 660 Route des Lucioles, Sophia Antipolis, 06560, Valbonne, France

    Sylviane Robineau, Sophie Béraud-Dufour, Bruno Antonny & Pierre Chardin

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Correspondence to Jacqueline Cherfils.

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Cherfils, J., Ménétrey, J., Mathieu, M. et al. Structure of the Sec7 domain of the Arf exchange factor ARNO. Nature 392, 101–105 (1998). https://doi.org/10.1038/32210

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