HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 39, 28834-28842, September 28, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/39/28834    most recent M705525200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ramaen, O. Articles by Cherfils, J. Search for Related Content PubMed PubMed Citation Articles by Ramaen, O. Articles by Cherfils, J. Social Bookmarking                      What's this?

Interactions between Conserved Domains within Homodimers in the BIG1, BIG2, and GBF1 Arf Guanine Nucleotide Exchange Factors^*

Odile Ramaen¹, Alexandra Joubert, Philip Simister¹, Naïma Belgareh-Touzé, Maria Conception Olivares-Sanchez², Jean-Christophe Zeeh, Sophie Chantalat, Marie-Pierre Golinelli-Cohen, Catherine L. Jackson, Valérie Biou, and Jacqueline Cherfils³

From the Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 91198 Gif-sur-Yvette, France and Institut Jacques Monod-CNRS, Universités Paris VI et VII, 75251 Paris, France

Guanine nucleotide exchange factors carrying a Sec7 domain (ArfGEFs) activate the small GTP-binding protein Arf, a major regulator of membrane remodeling and protein trafficking in eukaryotic cells. Only two of the seven subfamilies of ArfGEFs (GBF and BIG) are found in all eukaryotes. In addition to the Sec7 domain, which catalyzes GDP/GTP exchange on Arf, the GBF and BIG ArfGEFs have five common homology domains. Very little is known about the functions of these noncatalytic domains, but it is likely that they serve to integrate upstream signals that define the conditions of Arf activation. Here we describe interactions between two conserved domains upstream of the Sec7 domain (DCB and HUS) that determine the architecture of the N-terminal regions of the GBF and BIG ArfGEFs using a combination of biochemical, yeast two-hybrid, and cellular assays. Our data demonstrate a strong interaction between DCB domains within GBF1, BIG1, and BIG2 to maintain homodimers and an interaction between DCB and HUS domains within each homodimer. The DCB/HUS interaction is mediated by the HUS box, the most conserved motif in large ArfGEFs after the Sec7 domain. In support of the in vitro data, we show that both the DCB and the HUS domains are necessary for GBF1 dimerization in mammalian cells and that the DCB domain is essential for yeast viability. We propose that the dimeric DCB-HUS structural unit exists in all members of the GBF and BIG ArfGEF groups and in the related Mon2p family and probably serves an important regulatory role in Arf activation.

Received for publication, July 5, 2007

^* This work was supported by a Human Frontiers in Science Program grant and a French Ministère de la Recherche ACI grant (to J. C.) and a CNRS ATIP grant (to V. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by a grant from the CNRS.

² Supported by a Marie-Curie grant from the European Community.

³ To whom correspondence should be addressed: Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. Tel.: 33-1-6982-3492; Fax: 33-1-6982-3129; E-mail: cherfils{at}lebs.cnrs-gif.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. A. K. Dehring, A. S. Adler, A. Hosseini, and L. Hicke A C-terminal Sequence in the Guanine Nucleotide Exchange Factor Sec7 Mediates Golgi Association and Interaction with the Rsp5 Ubiquitin Ligase J. Biol. Chem., December 5, 2008; 283(49): 34188 - 34196. [Abstract] [Full Text] [PDF]

				H. Pan, J. Yu, L. Zhang, A. Carpenter, H. Zhu, L. Li, D. Ma, and J. Yuan A Novel Small Molecule Regulator of Guanine Nucleotide Exchange Activity of the ADP-ribosylation Factor and Golgi Membrane Trafficking J. Biol. Chem., November 7, 2008; 283(45): 31087 - 31096. [Abstract] [Full Text] [PDF]

				R. Ishizaki, H.-W. Shin, H. Mitsuhashi, and K. Nakayama Redundant Roles of BIG2 and BIG1, Guanine-Nucleotide Exchange Factors for ADP-Ribosylation Factors in Membrane Traffic between the trans-Golgi Network and Endosomes Mol. Biol. Cell, June 1, 2008; 19(6): 2650 - 2660. [Abstract] [Full Text] [PDF]

				N. Anders, M. Nielsen, J. Keicher, Y.-D. Stierhof, M. Furutani, M. Tasaka, K. Skriver, and G. Jurgens Membrane Association of the Arabidopsis ARF Exchange Factor GNOM Involves Interaction of Conserved Domains PLANT CELL, January 1, 2008; 20(1): 142 - 151. [Abstract] [Full Text] [PDF]