Structural highlights
Function
[RPGP1_HUMAN] GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state. [RAP1B_HUMAN] GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the establishment and maintenance of correct endothelial cell polarity and vascular lumen. Required for the localization of phosphorylated PRKCZ, PARD3 and TIAM1 to the cell junction.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
The Rap-RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues.,Scrima A, Thomas C, Deaconescu D, Wittinghofer A EMBO J. 2008 Apr 9;27(7):1145-53. Epub 2008 Feb 28. PMID:18309292[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lampugnani MG, Orsenigo F, Rudini N, Maddaluno L, Boulday G, Chapon F, Dejana E. CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J Cell Sci. 2010 Apr 1;123(Pt 7):1073-80. doi: 10.1242/jcs.059329. PMID:20332120 doi:10.1242/jcs.059329
- ↑ Rehmann H, Arias-Palomo E, Hadders MA, Schwede F, Llorca O, Bos JL. Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B. Nature. 2008 Sep 4;455(7209):124-7. Epub 2008 Jul 27. PMID:18660803 doi:http://dx.doi.org/10.1038/nature07187
- ↑ Scrima A, Thomas C, Deaconescu D, Wittinghofer A. The Rap-RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues. EMBO J. 2008 Apr 9;27(7):1145-53. Epub 2008 Feb 28. PMID:18309292 doi:10.1038/emboj.2008.30
