| Structural highlights
Function
[RAP2A_HUMAN] Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and may regulate cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading.[1] [2] [3] [4] [5] [6]
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
We report a novel crystal form of the small G protein Rap2A in complex with GTP which has no GTPase activity in the crystal. The asymmetric unit contains two complexes which show that a conserved switch I residue, Tyr 32, contributes an extra hydrogen bond to the gamma-phosphate of GTP as compared to related structures with GTP analogs. Since GTP is not hydrolyzed in the crystal, this interaction is unlikely to contribute to the intrinsic GTPase activity. The comparison of other G protein structures to the Rap2-GTP complex suggests that an equivalent interaction is likely to exist in their GTP form, whether unbound or bound to an effector. This interaction has to be released to allow the GAP-activated GTPase, and presumably the intrinsic GTPase activity as well. We also discuss the definition of the flexible regions and their hinges in the light of this structure and the expanding database of G protein structures. We propose that the switch I and switch II undergo either partial or complete disorder-to-order transitions according to their cellular status, thus defining a complex energy landscape comprising more than two conformational states. We observe in addition that the region connecting the switch I and switch II is flexible in Rap2 and other G proteins. This region may be important for protein-protein interactions and possibly behave as a conformational lever arm, as characterized for Arf. Taken together, these observations suggest that the structural mechanisms of small G proteins are significantly driven by entropy-based free energy changes.
Structure of the small G protein Rap2 in a non-catalytic complex with GTP.,Menetrey J, Cherfils J Proteins. 1999 Nov 15;37(3):465-73. PMID:10591105[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Machida N, Umikawa M, Takei K, Sakima N, Myagmar BE, Taira K, Uezato H, Ogawa Y, Kariya K. Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase. J Biol Chem. 2004 Apr 16;279(16):15711-4. Epub 2004 Feb 13. PMID:14966141 doi:10.1074/jbc.C300542200
- ↑ Taira K, Umikawa M, Takei K, Myagmar BE, Shinzato M, Machida N, Uezato H, Nonaka S, Kariya K. The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. J Biol Chem. 2004 Nov 19;279(47):49488-96. Epub 2004 Sep 1. PMID:15342639 doi:10.1074/jbc.M406370200
- ↑ Mittal V, Linder ME. Biochemical characterization of RGS14: RGS14 activity towards G-protein alpha subunits is independent of its binding to Rap2A. Biochem J. 2006 Feb 15;394(Pt 1):309-15. PMID:16246175 doi:10.1042/BJ20051086
- ↑ Greco F, Ciana A, Pietra D, Balduini C, Minetti G, Torti M. Rap2, but not Rap1 GTPase is expressed in human red blood cells and is involved in vesiculation. Biochim Biophys Acta. 2006 Mar;1763(3):330-5. Epub 2006 Feb 28. PMID:16540189 doi:10.1016/j.bbamcr.2006.02.001
- ↑ Nonaka H, Takei K, Umikawa M, Oshiro M, Kuninaka K, Bayarjargal M, Asato T, Yamashiro Y, Uechi Y, Endo S, Suzuki T, Kariya K. MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold protein TANC1. Biochem Biophys Res Commun. 2008 Dec 12;377(2):573-8. doi:, 10.1016/j.bbrc.2008.10.038. Epub 2008 Oct 18. PMID:18930710 doi:10.1016/j.bbrc.2008.10.038
- ↑ Kawabe H, Neeb A, Dimova K, Young SM Jr, Takeda M, Katsurabayashi S, Mitkovski M, Malakhova OA, Zhang DE, Umikawa M, Kariya K, Goebbels S, Nave KA, Rosenmund C, Jahn O, Rhee J, Brose N. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007. PMID:20159449 doi:10.1016/j.neuron.2010.01.007
- ↑ Menetrey J, Cherfils J. Structure of the small G protein Rap2 in a non-catalytic complex with GTP. Proteins. 1999 Nov 15;37(3):465-73. PMID:10591105
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