How RhoGDI binds Rho

Longenecker, K.L.; Read, Paul W.; Derewenda, Urszula; Dauter, Zbigniew; Liu, Xiaopu; Garrard, Sarah; Walker, Lori A.; Somlyo, Avril V.; Nakamoto, Robert K.; Somlyo, Andrew P.; Derewenda, Zygmunt S.

doi:10.1107/s090744499900801x

Cited by 75 publications

(64 citation statements)

References 38 publications

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“…We confirmed this finding directly, by the binding of recombinant ADP-ribosylated RhoA to recombinant GDI-1 thereby excluding the involvement of any additional factors. From the structure of the RhoA-GDI-1 complex can be deduced that the ADP-ribose at Asn-41 is directed to the solvent and may not hamper the formation of the complex (46). ADP-ribosylation, however, changes the binding properties of Rho to GDI-1.…”

Section: Discussionmentioning

confidence: 99%

Entrapment of Rho ADP-ribosylated by Clostridium botulinum C3 Exoenzyme in the Rho-Guanine Nucleotide Dissociation Inhibitor-1 Complex

Genth

Gerhard

Maeda

et al. 2003

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Entrapment of Rho ADP-ribosylated by Clostridium botulinum C3 Exoenzyme in the Rho-Guanine Nucleotide Dissociation Inhibitor-1 Complex

Genth

Gerhard

Maeda

et al. 2003

Journal of Biological Chemistry

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“…Alternatively, the SH3-SH2-SH3 domains of Vav (i.e., Vav-C) may recruit Rac.GDP indirectly, perhaps via DOCK180 or another protein interaction. Several groups have shown that the inactive form of Rac exists in a cytosolic complex with RhoGDI and that GEFs are unable to promote nucleotide exchange while Rac is in this complex (Hancock and Hall, 1993;Longenecker et al, 1999). Whether RhoGDI remains bound, or is induced to dissociate, for example, by the interaction with ezrin/radixin/ moesin family proteins (Takahashi et al, 1997), which are found at phagosomes (Defacque et al, 2000), is unknown.…”

Section: Discussionmentioning

confidence: 99%

Vav Regulates Activation of Rac but Not Cdc42 during FcγR-mediated Phagocytosis

Patel

Hall

Caron

2002

MBoC

119

107

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Phagocytosis is the process whereby cells direct the spatially localized, receptor-driven engulfment of particulate materials. It proceeds via remodeling of the actin cytoskeleton and shares many of the core cytoskeletal components involved in adhesion and migration. Small GTPases of the Rho family have been widely implicated in coordinating actin dynamics in response to extracellular signals and during diverse cellular processes, including phagocytosis, yet the mechanisms controlling their recruitment and activation are not known. We show herein that in response to ligation of Fc receptors for IgG (Fc␥R), the guanine nucleotide exchange factor Vav translocates to nascent phagosomes and catalyzes GTP loading on Rac, but not Cdc42. The Vav-induced Rac activation proceeds independently of Cdc42 function, suggesting distinct roles for each GTPase during engulfment. Moreover, inhibition of Vav exchange activity or of Cdc42 activity does not prevent Rac recruitment to sites of particle attachment. We conclude that Rac is recruited to Fc␥ membrane receptors in its inactive, GDP-bound state and that Vav regulates phagocytosis through subsequent catalysis of GDP/GTP exchange on Rac.

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“…Although some sample-to-sample variability in the amounts of peptides eluting at each point was seen, substantial dimer peaks were observed only in oxidized samples, and aggregates eluting at 9.0 ml were seen only in fresh, nonoxidized samples. mAU, milli-absorbance units exposed residues of RhoA (11,17,19,23,25,28) had little effect on the ability of the peptide to inhibit RSV (Fig. 6).…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of RhoA-Derived Peptides against Respiratory Syncytial Virus Is Dependent on Formation of Peptide Dimers

Budge

Lebowitz

Graham

2003

Antimicrob Agents Chemother

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A synthetic peptide containing amino acids 77 to 95 of the intracellular GTPase RhoA has previously been shown to inhibit replication of respiratory syncytial virus (RSV) in cultured cells. We show that residues 80 to 90 of RhoA are sufficient for this activity and that the cysteine residue at position 83 is critical. Further studies with an optimal peptide sequence containing amino acids 80 to 94 of RhoA revealed that the antiviral potency of the peptide is dependent on the oxidation of cysteine 83. Size-exclusion chromatography and sedimentation equilibrium studies of the peptide comprising residues 80 to 94 revealed that it is capable of forming aggregates in both reduced and oxidized states. A peptide (83A) in which the cysteine residue is replaced by an alanine does not form dimers or higher-order aggregates and did not inhibit RSV replication at any concentration tested. These data indicate that formation of peptide multimers is necessary for the antiviral activities of RhoA-derived peptides and suggest that the observed antiviral activities of these peptides may be unrelated to the biological functions of their parent molecule.Respiratory syncytial virus (RSV) is an enveloped, negativesense, single-stranded RNA virus of the Paramyxovirus family. It is the most important cause of lower respiratory tract infections in children worldwide and is a significant cause of morbidity and mortality among immunocompromised adults and the institutionalized elderly (4). RSV enters host cells by fusing its viral envelope with the host cell plasma membrane to allow penetration of the viral nucleocapsid. The processes of viral attachment and fusion are mediated by the viral glycoproteins, termed the fusion protein (F), glycoprotein (G), and the small hydrophobic protein (SH). While G and SH can increase the efficiency of the viral entry process, F alone is sufficient (10,13,27).It has previously been observed that RSV F can interact with the small GTPase RhoA (20) and that a peptide derived from the F-binding region of RhoA is able to block the entry of RSV into susceptible host cells (21). This peptide, which we termed peptide 77-95, comprises the linear peptide sequence corresponding to amino acids (aa) 77 to 95 of RhoA. On the basis of the observation that peptide 77-95 can interfere with binding of F to RhoA in an in vitro enzyme-linked immunosorbent assay (ELISA), it was originally hypothesized that peptide 77-95 may inhibit an interaction between RSV F and RhoA essential to F-mediated membrane fusion (21). However, an in vivo interaction between F and RhoA at the time of viral entry has not been demonstrated. In addition, other agents that should be capable of inhibiting a RhoA-F interaction, such as anti-RhoA antibodies and exogenous, purified RhoA, have no inhibitory effect on RSV entry (unpublished data). Thus, the ability of the RhoA-derived peptide to inhibit RSV entry may be unrelated to its ability to disrupt an in vitro F-RhoA interaction.The region from aa 77 to 95 of RhoA corresponds to an internal beta st...

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How RhoGDI binds Rho

Cited by 75 publications

References 38 publications

Entrapment of Rho ADP-ribosylated by Clostridium botulinum C3 Exoenzyme in the Rho-Guanine Nucleotide Dissociation Inhibitor-1 Complex

Entrapment of Rho ADP-ribosylated by Clostridium botulinum C3 Exoenzyme in the Rho-Guanine Nucleotide Dissociation Inhibitor-1 Complex

Vav Regulates Activation of Rac but Not Cdc42 during FcγR-mediated Phagocytosis

Antiviral Activity of RhoA-Derived Peptides against Respiratory Syncytial Virus Is Dependent on Formation of Peptide Dimers

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