The Rap–RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues
Open Access
- 28 February 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 27 (7), 1145-1153
- https://doi.org/10.1038/emboj.2008.30
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.Keywords
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