| Structural highlights
1z2a is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Gene: | Rab23 (Mus musculus) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[RAB23_MOUSE] Note=Defects in Rab23 are the cause of the open brain phenotype. Mice suffer from exencephaly and severe malformations of the spinal cord and the dorsal root ganglia, leading to complete embryonic lethality. In addition, mice display poorly developed eyes and polydactyly.[1]
Function
[RAB23_MOUSE] The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). Plays a role in autophagic vacuole assembly, and mediates defense against pathogens, such as S.aureus, by promoting their capture by autophagosomes that then merge with lysosomes (By similarity). Together with SUFU, prevents nuclear import of GLI1, and thereby inhibits GLI1 transcription factor activity. Regulates GLI1 in differentiating chondrocytes. Likewise, regulates GLI3 proteolytic processing and modulates GLI2 and GLI3 transcription factor activity.[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
Rab GTPases regulate all stages of membrane trafficking, including vesicle budding, cargo sorting, transport, tethering and fusion. In the inactive (GDP-bound) conformation, accessory factors facilitate the targeting of Rab GTPases to intracellular compartments. After nucleotide exchange to the active (GTP-bound) conformation, Rab GTPases interact with functionally diverse effectors including lipid kinases, motor proteins and tethering complexes. How effectors distinguish between homologous Rab GTPases represents an unresolved problem with respect to the specificity of vesicular trafficking. Using a structural proteomic approach, we have determined the specificity and structural basis underlying the interaction of the multivalent effector rabenosyn-5 with the Rab family. The results demonstrate that even the structurally similar effector domains in rabenosyn-5 can achieve highly selective recognition of distinct subsets of Rab GTPases exclusively through interactions with the switch and interswitch regions. The observed specificity is determined at a family-wide level by structural diversity in the active conformation, which governs the spatial disposition of critical conserved recognition determinants, and by a small number of both positive and negative sequence determinants that allow further discrimination between Rab GTPases with similar switch conformations.
Structural basis of family-wide Rab GTPase recognition by rabenosyn-5.,Eathiraj S, Pan X, Ritacco C, Lambright DG Nature. 2005 Jul 21;436(7049):415-9. PMID:16034420[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gunther T, Struwe M, Aguzzi A, Schughart K. Open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord. Development. 1994 Nov;120(11):3119-30. PMID:7720556
- ↑ Gunther T, Struwe M, Aguzzi A, Schughart K. Open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord. Development. 1994 Nov;120(11):3119-30. PMID:7720556
- ↑ Eggenschwiler JT, Anderson KV. Dorsal and lateral fates in the mouse neural tube require the cell-autonomous activity of the open brain gene. Dev Biol. 2000 Nov 15;227(2):648-60. PMID:11071781 doi:10.1006/dbio.2000.9918
- ↑ Eggenschwiler JT, Espinoza E, Anderson KV. Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature. 2001 Jul 12;412(6843):194-8. PMID:11449277 doi:10.1038/35084089
- ↑ Eggenschwiler JT, Bulgakov OV, Qin J, Li T, Anderson KV. Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins. Dev Biol. 2006 Feb 1;290(1):1-12. Epub 2005 Dec 20. PMID:16364285 doi:10.1016/j.ydbio.2005.09.022
- ↑ Yang L, Clinton JM, Blackburn ML, Zhang Q, Zou J, Zielinska-Kwiatkowska A, Tang BL, Chansky HA. Rab23 regulates differentiation of ATDC5 chondroprogenitor cells. J Biol Chem. 2008 Apr 18;283(16):10649-57. doi: 10.1074/jbc.M706795200. Epub 2008, Jan 23. PMID:18218620 doi:10.1074/jbc.M706795200
- ↑ Eathiraj S, Pan X, Ritacco C, Lambright DG. Structural basis of family-wide Rab GTPase recognition by rabenosyn-5. Nature. 2005 Jul 21;436(7049):415-9. PMID:16034420 doi:http://dx.doi.org/10.1038/nature03798
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