1re0
From Proteopedia
Structure of ARF1-GDP bound to Sec7 domain complexed with Brefeldin A
Structural highlights
Function[ARF1_HUMAN] GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking among different compartments. Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles. [GEA1_YEAST] Activates the ARF proteins by exchanging bound GDP for free GTP. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedARF 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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