The structure of RalF, an ADP-ribosylation factor guanine nucleotide exchange factor from Legionella pneumophila, reveals the presence of a cap over the active site
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Amor, JC
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机构:Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
Amor, JC
Swails, J
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机构:Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
Swails, J
Zhu, XJ
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机构:Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
Zhu, XJ
Roy, CR
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机构:Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
Roy, CR
Nagai, H
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机构:Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
Nagai, H
Ingmundson, A
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机构:Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
Ingmundson, A
Cheng, XD
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机构:Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
Cheng, XD
Kahn, RA
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机构:Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
Kahn, RA
机构:
[1] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
[2] Yale Univ, Sch Med, Boyer Ctr Mol Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA
The Legionella pneumophila protein RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine nucleotide exchange factors, has suggested that recruitment of Arf is an early step in pathogenesis. We have determined the crystal structure of RalF and of the isolated Sec7 domain and found that RalF is made up of two domains. The Sec7 domain is homologous to mammalian Sec7 domains. The C-terminal domain forms a cap over the active site in the Sec7 domain and contains a conserved folding motif, previously observed in adaptor subunits of vesicle coat complexes. The importance of the capping domain and of the glutamate in the "glutamic finger," conserved in all Sec7 domains, to RalF functions was examined using three different assays. These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities.