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| | ==Structural and thermodynamic characterization of cadherin-beta-catenin-alpha-catenin complex formation== | | ==Structural and thermodynamic characterization of cadherin-beta-catenin-alpha-catenin complex formation== |
| - | <StructureSection load='4ons' size='340' side='right' caption='[[4ons]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4ons' size='340' side='right'caption='[[4ons]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ons]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ONS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ONS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ons]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ONS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ONS FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ctnna2, Catna2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Ctnnb1, Catnb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ons FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ons OCA], [https://pdbe.org/4ons PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ons RCSB], [https://www.ebi.ac.uk/pdbsum/4ons PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ons ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ons FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ons OCA], [http://pdbe.org/4ons PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ons RCSB], [http://www.ebi.ac.uk/pdbsum/4ons PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ons ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CTNA2_MOUSE CTNA2_MOUSE]] May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation.<ref>PMID:12089526</ref> <ref>PMID:12123610</ref> <ref>PMID:15034585</ref> [[http://www.uniprot.org/uniprot/CTNB1_MOUSE CTNB1_MOUSE]] Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (By similarity). | + | [https://www.uniprot.org/uniprot/CTNA2_MOUSE CTNA2_MOUSE] May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation.<ref>PMID:12089526</ref> <ref>PMID:12123610</ref> <ref>PMID:15034585</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Catenin|Catenin]] | + | *[[Catenin 3D structures|Catenin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Ahlsen, G]] | + | [[Category: Mus musculus]] |
| - | [[Category: Choi, H J]] | + | [[Category: Ahlsen G]] |
| - | [[Category: Hansen, S D]] | + | [[Category: Choi H-J]] |
| - | [[Category: Pokutta, S]] | + | [[Category: Hansen SD]] |
| - | [[Category: Weis, W I]] | + | [[Category: Pokutta S]] |
| - | [[Category: Cell adhesion]]
| + | [[Category: Weis WI]] |
| - | [[Category: Four helix bundle]]
| + | |
| Structural highlights
Function
CTNA2_MOUSE May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation.[1] [2] [3]
Publication Abstract from PubMed
The classical cadherin-beta-catenin-alpha-catenin complex mediates homophilic cell-cell adhesion and mechanically couples the actin cytoskeletons of adjacent cells. Although alpha-catenin binds to beta-catenin and to F-actin, beta-catenin significantly weakens the affinity of alpha-catenin for F-actin. Moreover, alpha-catenin self-associates into homodimers that block beta-catenin binding. We investigated quantitatively and structurally alphaE- and alphaN-catenin dimer formation, their interaction with beta-catenin and the cadherin-beta-catenin complex, and the effect of the alpha-catenin actin-binding domain on beta-catenin association. The two alpha-catenin variants differ in their self-association properties: at physiological temperatures alphaE-catenin homodimerizes 10x more weakly than does alphaN-catenin, but is kinetically trapped in its oligomeric state. Both alphaE- and alphaN-catenin bind to beta-catenin with a Kd of 20 nM, and this affinity is increased by an order of magnitude when cadherin is bound to beta-catenin. We describe the crystal structure of a complex representing the full beta-catenin-alphaN-catenin interface. A three-dimensional model of the cadherin-beta-catenin-alpha-catenin complex based on these new structural data suggests mechanisms for the enhanced stability of the ternary complex. The C-terminal actin-binding domain of alpha-catenin has no influence on the interactions with beta-catenin, arguing against models in which beta-catenin weakens actin binding by stabilizing inhibitory intramolecular interactions between the actin-binding domain and the rest of alpha-catenin.
Structural and Thermodynamic Characterization of Cadherin-beta-catenin-alpha-catenin Complex Formation.,Pokutta S, Choi HJ, Ahlsen G, Hansen SD, Weis WI J Biol Chem. 2014 Apr 1. PMID:24692547[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Park C, Falls W, Finger JH, Longo-Guess CM, Ackerman SL. Deletion in Catna2, encoding alpha N-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation. Nat Genet. 2002 Jul;31(3):279-84. Epub 2002 Jun 24. PMID:12089526 doi:10.1038/ng908
- ↑ Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M. Cadherin regulates dendritic spine morphogenesis. Neuron. 2002 Jul 3;35(1):77-89. PMID:12123610
- ↑ Abe K, Chisaka O, Van Roy F, Takeichi M. Stability of dendritic spines and synaptic contacts is controlled by alpha N-catenin. Nat Neurosci. 2004 Apr;7(4):357-63. Epub 2004 Mar 21. PMID:15034585 doi:10.1038/nn1212
- ↑ Pokutta S, Choi HJ, Ahlsen G, Hansen SD, Weis WI. Structural and Thermodynamic Characterization of Cadherin-beta-catenin-alpha-catenin Complex Formation. J Biol Chem. 2014 Apr 1. PMID:24692547 doi:http://dx.doi.org/10.1074/jbc.M114.554709
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