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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2003-12-23
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1403-11
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:14690595-ADP-Ribosylation Factor 1,
pubmed-meshheading:14690595-Binding Sites,
pubmed-meshheading:14690595-Brefeldin A,
pubmed-meshheading:14690595-Crystallography, X-Ray,
pubmed-meshheading:14690595-Enzyme Activation,
pubmed-meshheading:14690595-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:14690595-Guanosine Diphosphate,
pubmed-meshheading:14690595-Guanosine Triphosphate,
pubmed-meshheading:14690595-Humans,
pubmed-meshheading:14690595-Macromolecular Substances,
pubmed-meshheading:14690595-Models, Molecular,
pubmed-meshheading:14690595-Protein Structure, Quaternary,
pubmed-meshheading:14690595-Protein Synthesis Inhibitors
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pubmed:year |
2003
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pubmed:articleTitle |
Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism.
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pubmed:affiliation |
Howard Hughes Medical Institute, Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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