The GTPase-activating protein Rap1GAP uses a catalytic asparagine

@article{Daumke2004TheGP,
  title={The GTPase-activating protein Rap1GAP uses a catalytic asparagine},
  author={O. Daumke and M. Weyand and P. Chakrabarti and I. Vetter and A. Wittinghofer},
  journal={Nature},
  year={2004},
  volume={429},
  pages={197-201}
}
Rap1 is a Ras-like guanine-nucleotide-binding protein (GNBP) that is involved in a variety of signal-transduction processes. It regulates integrin-mediated cell adhesion and might activate extracellular signal-regulated kinase. Like other Ras-like GNBPs, Rap1 is regulated by guanine-nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs). These GAPs increase the slow intrinsic GTPase reaction of Ras-like GNBPs by many orders of magnitude and allow tight regulation of signalling… Expand
The Rap–RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues
TLDR
The structure and biochemical data allow to further explain the mechanism and to define the important role of a conserved tyrosine and the RapGAP homologous region of the tumour suppressor Tuberin is sufficient for catalysis on Rheb. Expand
GTPase activity of Di-Ras proteins is stimulated by Rap1GAP proteins
TLDR
The Ras family is the largest and most diverse sub-group of Ras-like G proteins, and the high number of regulatory Guanine nucleotide Exchange Factors (GEFs) and GTPase activating proteins (GAPs) that target specific members of this subfamily are increased. Expand
The GAP1 family of GTPase-activating proteins: spatial and temporal regulators of small GTPase signalling.
TLDR
A group of key regulators of Ras inactivation, the GAP1 family of Ras-GAPs, are emerging as important modulators of Ras and small GTPase signalling that are subject to regulation by a diverse array of events and second messenger signals. Expand
Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets.
TLDR
Rap1GAP2 is the first GTPase-activating protein of Rap1 found in platelets and is likely to have an important regulatory role in platelet aggregation and may mediate inhibitory effects of NO/cGMP on Rap1. Expand
Structure and Function of the mTOR Activator Rheb
Ras homologue enriched in brain (Rheb) is a well-known activator of the mammalian target of rapamycin (mTOR) protein kinase. It is a highly conserved small GTPase protein that is ubiquitouslyExpand
The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction
TLDR
SynGAP presents the first example of a GAP that uses a second domain for catalytic activity, thus pointing to a new function of C2 domains, and supports a catalytic mechanism similar to that of canonical RasGAPs and distinct from the canonical RapG APs. Expand
Fourier Transform Infrared Spectroscopy on the Rap·RapGAP Reaction, GTPase Activation without an Arginine Finger*
TLDR
The Rap·RapGAP catalytic machinery compensates for the absence of a cis-Gln by a trans-Asn and for the catalytic Arg by inducing a different GTP conformation that is more prone to be attacked by a water molecule. Expand
Structural basis for the molecular evolution of SRP-GTPase activation by protein
TLDR
This study exemplifies the evolutionary transition from RNA- to protein-driven activation in SRP-GTPases and suggests that the current view onSRP-mediated protein targeting is incomplete. Expand
Differential G-alpha interaction capacities of the GoLoco motifs in Rap GTPase activating proteins.
TLDR
It is found that human Rap1GAP2b/c was deficient in GDI activity and Galpha interaction capability and can be classed as inactive towards Galpha subunits. Expand
Probing the GTPase cycle with real-time NMR: GAP and GEF activities in cell extracts.
TLDR
A recently developed real-time NMR method is described that makes it possible to precisely measure GAP and GEF activities from extracts of mammalian cells, enabling studies of their catalytic and regulatory mechanisms. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 33 REFERENCES
Rap-specific GTPase Activating Protein follows an Alternative Mechanism*
TLDR
This study supports the notion of a completely different mechanism of the Rap1GAP-catalyzed GTP-hydrolysis reaction on Rap1, which is shown to be efficiently down-regulated by Rap1 GAP. Expand
RanGAP mediates GTP hydrolysis without an arginine finger
TLDR
The structure and biochemical experiments show that RanGAP does not act through an arginine finger, that the basic machinery for fast GTP hydrolysis is provided exclusively by Ran and that correct positioning of the catalytic glutamine is essential for catalysis. Expand
Magnesium fluoride-dependent binding of small G proteins to their GTPase-activating proteins.
TLDR
Equilibrium binding has been measured using scintillation proximity assays to provide quantitative information on the fluoride-mediated interaction of Ras and Rho proteins with their respective GAPs, neurofibromin (NF1) and RHoGAP, and these data suggest that some protein. Expand
The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.
TLDR
The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations. Expand
Localization of the rap1GAP catalytic domain and sites of phosphorylation by mutational analysis.
TLDR
Analysis of the purified mutant proteins shows that of 663 amino acid residues, only amino acids 75 to 416 are necessary for full GAP activity, whereas removal of additional carboxy-terminal residues dramatically accelerated the degradation of the protein in vivo. Expand
Fluorescently labelled guanine nucleotide binding proteins to analyse elementary steps of GAP-catalysed reactions.
TLDR
The data reveal marked differences in GAP/target interactions even between closely related systems and suggest that the fluorescent reporter group method might be generally applicable to many other GNBPs and their cognate GAPs. Expand
Structure at 1.65 Å of RhoA and its GTPase-activating protein in complex with a transition-state analogue
TLDR
The crystal structure of RhoA and rhoGAP complexed with the transition-state analogue GDP is reported and it is proposed that this residue acts to stabilize the transition state of the GTPase reaction. Expand
Rap1 GTPase: functions, regulation, and malignancy.
TLDR
Rap1 is a member of the Ras family of small GTPases that is activated by diverse extracellular stimuli in many cell types and playing important roles in the regulation of a variety of integrin-dependent cellular functions. Expand
Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP
TLDR
Comparison of the structures for the wild type and mutant Cdc42GAP complexes provides important insights into the GAP-catalyzed GTP hydrolytic reaction. Expand
Guanine nucleotide binding properties of Rac2 mutant proteins and analysis of the responsiveness to guanine nucleotide dissociation stimulator.
TLDR
It is shown that guanine nucleotide exchange by smgGDS is dependent upon intact switch 1 and switch 2 regions in Rac2 and form the basis for rational use of Rac mutants in biological studies. Expand
...
1
2
3
4
...