1re0
From Proteopedia
Structure of ARF1-GDP bound to Sec7 domain complexed with Brefeldin A
Overview
ARF GTPases are activated by guanine nucleotide exchange factors (GEFs) of the Sec7 family that promote the exchange of GDP for GTP. Brefeldin A (BFA) is a fungal metabolite that binds to the ARF1*GDP*Sec7 complex and blocks GEF activity at an early stage of the reaction, prior to guanine nucleotide release. The crystal structure of the ARF1*GDP*Sec7*BFA complex shows that BFA binds at the protein-protein interface to inhibit conformational changes in ARF1 required for Sec7 to dislodge the GDP molecule. Based on a comparative analysis of the inhibited complex, nucleotide-free ARF1*Sec7 and ARF1*GDP, we suggest that, in addition to forcing nucleotide release, the ARF1-Sec7 binding energy is used to open a cavity on ARF1 to facilitate the rearrangement of hydrophobic core residues between the GDP and GTP conformations. Thus, the Sec7 domain may act as a dual catalyst, facilitating both nucleotide release and conformational switching on ARF proteins.
About this Structure
1RE0 is a Protein complex structure of sequences from Homo sapiens and Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism., Mossessova E, Corpina RA, Goldberg J, Mol Cell. 2003 Dec;12(6):1403-11. PMID:14690595 Page seeded by OCA on Sat May 3 07:22:56 2008
