Cited by 127Protein Kinase Regulation and GTPase SignalingCellular transport and secretionReceptor Mechanisms and Signaling

The Rap–RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues

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Scrima, Andrea, Thomas, Christoph, Deaconescu, Delia, Wittinghofer, Alfred·2008·The EMBO Journal

Abstract

The GTP-binding protein Rap1 regulates integrin-mediated and other cell adhesion processes. Unlike most other Ras-related proteins, it contains a threonine in switch II instead of a glutamine (Gln61 in Ras), a residue crucial for the GTPase reaction of most G proteins. Furthermore, unlike most other GTPase-activating proteins (GAPs) for small G proteins, which supply a catalytically important Arg-finger, no arginine residue of RapGAP makes a significant contribution to the GTPase reaction of Rap1. For a detailed understanding of the reaction mechanism, we have solved the structure of Rap1 in complex with Rap1GAP. It shows that the Thr61 of Rap is away from the active site and that an invariant asparagine of RapGAPs, the Asn-thumb, takes over the role of the cis-glutamine of Ras, Rho or Ran. The structure and biochemical data allow to further explain the mechanism and to define the important role of a conserved tyrosine. The structure and biochemical data furthermore show that the RapGAP homologous region of the tumour suppressor Tuberin is sufficient for catalysis on Rheb.

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Crossref · 10.1038/emboj.2008.30

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  • The TSC2 GAP domain utilizes an "asparagine-thumb" mechanism for the activation of Rheb GTPase activity, similar to that of the Rap GTPase and its GAP.

    “It is known that the TSC2 GAP domain utilizes an “asparagine-thumb” mechanism for the activation of Rheb GTPase activity, similar to that of the Rap GTPase and its GAP (Marshall et al., 2009; Scrima et al., 2008)”

    From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Scrima et al., 2008

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Authors
Scrima, A., Thomas, C., Deaconescu, D., & Wittinghofer, A.
Affiliations
  • Max Planck Institute of Molecular Physiology (DE)
  • Max Planck Society (DE)
Corresponding author
Wittinghofer, Alfred
Venue
The EMBO Journal
Published
2008-02-28
Volume
27
Issue
7
Pages
1145-1153
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2104235973
Cited by
127
References
36
Citations by year
2026: 3 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 2 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 4 · 2014: 8 · 2013: 8 · 2012: 19
FWCI
4.11
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
Paul Scherrer Institut
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
Rap1, Rap1GAP, GTPase-activating protein, arginine finger, integrin-mediated adhesion, tuberin, Rheb
MeSH terms
Tuberous Sclerosis Complex 2 Protein, Amino Acid Sequence, Arginine, Binding Sites, Catalysis, Glutamine, Guanosine Triphosphate, Hydrolysis, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Crystallography, X-Ray, GTPase-Activating Proteins, rap1 GTP-Binding Proteins, Tumor Suppressor Proteins, Mutant Proteins

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