| Structural highlights
2dfk is a 4 chain structure with sequence from Buffalo rat and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 1foe, 1kz7, 1kzg, 1lb1, 1ki1, 1dbh |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ARHG9_RAT] Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters.[1] [2] [3] [CDC42_HUMAN] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.[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
The synaptic localization of ion channel receptors is essential for efficient synaptic transmission and the precise regulation of diverse neuronal functions. In the central nervous system, ion channel receptors reside in the postsynaptic membrane where they are juxtaposed to presynaptic terminals. For proper function, these ion channels have to be anchored to the cytoskeleton, and in the case of the inhibitory glycine and gamma-amino-butyric acid type A (GABA(A)) receptors this interaction is mediated by a gephyrin centered scaffold. Highlighting its central role in this receptor anchoring scaffold, gephyrin interacts with a number of proteins, including the neurospecific guanine nucleotide exchange factor collybistin. Collybistin belongs to the Dbl family of guanine nucleotide exchange factors, occurs in multiple splice variants, and is specific for Cdc42, a small GTPase belonging to the Rho family. The 2.3 Angstroms resolution crystal structure of the Cdc42-collybistin II complex reveals a novel conformation of the switch I region of Cdc42. It also provides the first direct observation of structural changes in the relative orientation of the Dbl-homology domain and the pleckstrin-homology domain in the same Dbl family protein. Biochemical data indicate that gephyrin negatively regulates collybistin activity.
The crystal structure of Cdc42 in complex with collybistin II, a gephyrin-interacting guanine nucleotide exchange factor.,Xiang S, Kim EY, Connelly JJ, Nassar N, Kirsch J, Winking J, Schwarz G, Schindelin H J Mol Biol. 2006 May 26;359(1):35-46. Epub 2006 Mar 29. PMID:16616186[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kins S, Betz H, Kirsch J. Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin. Nat Neurosci. 2000 Jan;3(1):22-9. PMID:10607391 doi:http://dx.doi.org/10.1038/71096
- ↑ Grosskreutz Y, Hermann A, Kins S, Fuhrmann JC, Betz H, Kneussel M. Identification of a gephyrin-binding motif in the GDP/GTP exchange factor collybistin. Biol Chem. 2001 Oct;382(10):1455-62. PMID:11727829 doi:http://dx.doi.org/10.1515/BC.2001.179
- ↑ Harvey K, Duguid IC, Alldred MJ, Beatty SE, Ward H, Keep NH, Lingenfelter SE, Pearce BR, Lundgren J, Owen MJ, Smart TG, Luscher B, Rees MI, Harvey RJ. The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering. J Neurosci. 2004 Jun 23;24(25):5816-26. PMID:15215304 doi:10.1523/JNEUROSCI.1184-04.2004
- ↑ Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004 May;15(5):2205-17. Epub 2004 Feb 20. PMID:14978216 doi:10.1091/mbc.E03-07-0493
- ↑ Oceguera-Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, Haraguchi T, Narumiya S. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol. 2005 Jan 17;168(2):221-32. Epub 2005 Jan 10. PMID:15642749 doi:10.1083/jcb.200408085
- ↑ Modzelewska K, Newman LP, Desai R, Keely PJ. Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12. PMID:17038317 doi:10.1074/jbc.M604342200
- ↑ Xiang S, Kim EY, Connelly JJ, Nassar N, Kirsch J, Winking J, Schwarz G, Schindelin H. The crystal structure of Cdc42 in complex with collybistin II, a gephyrin-interacting guanine nucleotide exchange factor. J Mol Biol. 2006 May 26;359(1):35-46. Epub 2006 Mar 29. PMID:16616186 doi:10.1016/j.jmb.2006.03.019
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