1re0

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spinqualitylabelsall models 1re0, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 with , , and as ligands. 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

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