Proteopedia

2f0a

Crystal Structure of Monomeric Uncomplexed form of Xenopus dishevelled PDZ domainCrystal Structure of Monomeric Uncomplexed form of Xenopus dishevelled PDZ domain

Structural highlights

2f0a is a 4 chain structure with sequence from Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DVL2_XENLA Involved in at least 2 independent signaling cascades, controlling cell fate via canonical Wnt signaling and cell polarity via a planar cell polarity (PCP) cascade. Acts synergistically with dal/dapple-like to activate Wnt signaling, stabilizing ctnnb1/beta-catenin and leading to dorsal axis formation. Also prevents degradation of ctnnb1/beta-catenin by displacing gsk3 from a complex with ARP/Axin-related protein. Has an additional role in anterior-posterior (A/P) axis formation, specifying different neuroectodermal cell fates along the A/P axis in a dose-dependent manner by activating several early patterning genes. In the PCP pathway, required at the cell membrane for PCP-mediated neural and mesodermal convergent extension during gastrulation and subsequent neural tube closure, acting to activate jnk. Also involved in blastopore closure and archenteron elongation during early, but not late, gastrulation. Associates with ephrin receptors and ligands and acts as part of a downstream PCP pathway to mediate ephrin-mediated cell repulsion via activation of rhoa. Required for efnb1/ephrin-B1-driven movement of non-retinal progenitor cells into the retina during eye field formation. Patterns the hindbrain. Required for ciliogenesis. Controls the docking of basal bodies to the apical plasma membrane; mediates the activation, but not localization of rhoa at the apical surface of ciliated cells during basal body docking. Furthermore, required for the association of basal bodies with membrane-bound vesicles and the vesicle-trafficking protein exoc4/sec8, and this association is in turn required for basal body docking. Once basal bodies are docked, required for the planar polarization of basal bodies that underlies ciliary beating and the directional fluid flow across ciliated epithelia.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Sokol SY, Klingensmith J, Perrimon N, Itoh K. Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled. Development. 1995 Jun;121(6):1637-47. PMID:7600981
  2. ↑ Sokol SY. Analysis of Dishevelled signalling pathways during Xenopus development. Curr Biol. 1996 Nov 1;6(11):1456-67. PMID:8939601
  3. ↑ Itoh K, Sokol SY. Graded amounts of Xenopus dishevelled specify discrete anteroposterior cell fates in prospective ectoderm. Mech Dev. 1997 Jan;61(1-2):113-25. PMID:9076682
  4. ↑ Miller JR, Rowning BA, Larabell CA, Yang-Snyder JA, Bates RL, Moon RT. Establishment of the dorsal-ventral axis in Xenopus embryos coincides with the dorsal enrichment of dishevelled that is dependent on cortical rotation. J Cell Biol. 1999 Jul 26;146(2):427-37. PMID:10427095
  5. ↑ Itoh K, Antipova A, Ratcliffe MJ, Sokol S. Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction. Mol Cell Biol. 2000 Mar;20(6):2228-38. PMID:10688669
  6. ↑ Wallingford JB, Rowning BA, Vogeli KM, Rothbacher U, Fraser SE, Harland RM. Dishevelled controls cell polarity during Xenopus gastrulation. Nature. 2000 May 4;405(6782):81-5. PMID:10811222 doi:http://dx.doi.org/10.1038/35011077
  7. ↑ Wallingford JB, Harland RM. Xenopus Dishevelled signaling regulates both neural and mesodermal convergent extension: parallel forces elongating the body axis. Development. 2001 Jul;128(13):2581-92. PMID:11493574
  8. ↑ Wallingford JB, Harland RM. Neural tube closure requires Dishevelled-dependent convergent extension of the midline. Development. 2002 Dec;129(24):5815-25. PMID:12421719
  9. ↑ Gloy J, Hikasa H, Sokol SY. Frodo interacts with Dishevelled to transduce Wnt signals. Nat Cell Biol. 2002 May;4(5):351-7. PMID:11941372 doi:http://dx.doi.org/10.1038/ncb784
  10. ↑ Tanaka M, Kamo T, Ota S, Sugimura H. Association of Dishevelled with Eph tyrosine kinase receptor and ephrin mediates cell repulsion. EMBO J. 2003 Feb 17;22(4):847-58. PMID:12574121 doi:http://dx.doi.org/10.1093/emboj/cdg088
  11. ↑ Ewald AJ, Peyrot SM, Tyszka JM, Fraser SE, Wallingford JB. Regional requirements for Dishevelled signaling during Xenopus gastrulation: separable effects on blastopore closure, mesendoderm internalization and archenteron formation. Development. 2004 Dec;131(24):6195-209. Epub 2004 Nov 17. PMID:15548584 doi:http://dx.doi.org/dev.01542
  12. ↑ Park TJ, Gray RS, Sato A, Habas R, Wallingford JB. Subcellular localization and signaling properties of dishevelled in developing vertebrate embryos. Curr Biol. 2005 Jun 7;15(11):1039-44. PMID:15936275 doi:http://dx.doi.org/S0960-9822(05)00509-9
  13. ↑ Kobayashi H, Michiue T, Yukita A, Danno H, Sakurai K, Fukui A, Kikuchi A, Asashima M. Novel Daple-like protein positively regulates both the Wnt/beta-catenin pathway and the Wnt/JNK pathway in Xenopus. Mech Dev. 2005 Oct;122(10):1138-53. PMID:16026968 doi:http://dx.doi.org/S0925-4773(05)00077-8
  14. ↑ Liu J, Bang AG, Kintner C, Orth AP, Chanda SK, Ding S, Schultz PG. Identification of the Wnt signaling activator leucine-rich repeat in Flightless interaction protein 2 by a genome-wide functional analysis. Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1927-32. Epub 2005 Jan 26. PMID:15677333 doi:http://dx.doi.org/10.1073/pnas.0409472102
  15. ↑ Lee HS, Bong YS, Moore KB, Soria K, Moody SA, Daar IO. Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway. Nat Cell Biol. 2006 Jan;8(1):55-63. Epub 2005 Dec 18. PMID:16362052 doi:http://dx.doi.org/10.1038/ncb1344
  16. ↑ Park TJ, Mitchell BJ, Abitua PB, Kintner C, Wallingford JB. Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells. Nat Genet. 2008 Jul;40(7):871-9. doi: 10.1038/ng.104. Epub 2008 Jun 15. PMID:18552847 doi:http://dx.doi.org/10.1038/ng.104
  17. ↑ Cheyette BN, Waxman JS, Miller JR, Takemaru K, Sheldahl LC, Khlebtsova N, Fox EP, Earnest T, Moon RT. Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation. Dev Cell. 2002 Apr;2(4):449-61. PMID:11970895

2f0a, resolution 1.80Å

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