Interactions between conserved domains within homodimers in the BIG1, BIG2, and GBF1 Arf guanine nucleotide exchange factors. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2007

Interactions between conserved domains within homodimers in the BIG1, BIG2, and GBF1 Arf guanine nucleotide exchange factors.

Résumé

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 that 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 non-catalytic 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 of 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 catalytic 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 likely serves an important regulatory role in Arf activation.
Fichier principal
Vignette du fichier
Ramaen 2007.pdf (1.57 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01873531 , version 1 (13-09-2018)

Identifiants

Citer

Odile Ramaen, Alexandra Joubert, Philip Simister, Naïma Belgareh-Touzé, Maria Conception Olivares-Sanchez, et al.. Interactions between conserved domains within homodimers in the BIG1, BIG2, and GBF1 Arf guanine nucleotide exchange factors.. Journal of Biological Chemistry, 2007, ⟨10.1074/jbc.M705525200⟩. ⟨hal-01873531⟩
167 Consultations
74 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More