1RE0

Structure of ARF1-GDP bound to Sec7 domain complexed with Brefeldin A

Summary for 1RE0

• Entry DOI: 10.2210/pdb1re0/pdb
• Descriptor: ADP-ribosylation factor 1, ARF guanine-nucleotide exchange factor 1, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: all-helical, alph-beta, protein transport
• Biological source: Homo sapiens (human); More
• Cellular location: Golgi apparatus: P32889; Cytoplasm, cytosol: P47102
• Total number of polymer chains: 2
• Total formula weight: 45181.36

Authors

Goldberg, J.,Mossessova, E. (deposition date: 2003-11-06, release date: 2003-12-16, Last modification date: 2024-02-14)

Primary citation

Mossessova, E.,Corpina, R.A.,Goldberg, J.
Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism.
Mol.Cell, 12:1403-1411, 2003

PubMed Abstract: 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.

PubMed: 14690595
DOI: 10.1016/S1097-2765(03)00475-1

Experimental method

X-RAY DIFFRACTION (2.4 Å)