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| | ==Crystal Structure of Zebrafish Protocadherin-19 EC1-4== | | ==Crystal Structure of Zebrafish Protocadherin-19 EC1-4== |
| - | <StructureSection load='5iu9' size='340' side='right' caption='[[5iu9]], [[Resolution|resolution]] 3.59Å' scene=''> | + | <StructureSection load='5iu9' size='340' side='right'caption='[[5iu9]], [[Resolution|resolution]] 3.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5iu9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IU9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IU9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5iu9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IU9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IU9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.59Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pcdh19 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=5iu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iu9 OCA], [http://pdbe.org/5iu9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iu9 RCSB], [http://www.ebi.ac.uk/pdbsum/5iu9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iu9 ProSAT]</span></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=5iu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iu9 OCA], [https://pdbe.org/5iu9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iu9 RCSB], [https://www.ebi.ac.uk/pdbsum/5iu9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iu9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PCD19_DANRE PCD19_DANRE] Calcium-dependent cell-adhesion protein (PubMed:21115806). Essential for the early stages of neurulation in the anterior neural plate (PubMed:19615992). Shows little cell adhesion activity on its own but exhibits robust homophilic cell adhesion when in a complex with cadherin cdh2 and appears to mediate the adhesion while cdh2 acts as a cell adhesion cofactor in the complex (PubMed:21115806, PubMed:22184198, PubMed:33004519). Functions with cdh2 to coordinate cell adhesion and cell movements during neurulation (PubMed:21115806). Contributes to neural progenitor cell patterning with cdh2 by promoting homophilic cell interactions (PubMed:33004519). Regulates the columnar organization of neurons in the optic tectum (PubMed:26598617).<ref>PMID:19615992</ref> <ref>PMID:21115806</ref> <ref>PMID:22184198</ref> <ref>PMID:26598617</ref> <ref>PMID:33004519</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[Category: Cooper, S R]] | + | [[Category: Large Structures]] |
| - | [[Category: Jontes, J D]] | + | [[Category: Cooper SR]] |
| - | [[Category: Sotomayor, M]] | + | [[Category: Jontes JD]] |
| - | [[Category: Adhesion]] | + | [[Category: Sotomayor M]] |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Epilepsy]]
| + | |
| Structural highlights
Function
PCD19_DANRE Calcium-dependent cell-adhesion protein (PubMed:21115806). Essential for the early stages of neurulation in the anterior neural plate (PubMed:19615992). Shows little cell adhesion activity on its own but exhibits robust homophilic cell adhesion when in a complex with cadherin cdh2 and appears to mediate the adhesion while cdh2 acts as a cell adhesion cofactor in the complex (PubMed:21115806, PubMed:22184198, PubMed:33004519). Functions with cdh2 to coordinate cell adhesion and cell movements during neurulation (PubMed:21115806). Contributes to neural progenitor cell patterning with cdh2 by promoting homophilic cell interactions (PubMed:33004519). Regulates the columnar organization of neurons in the optic tectum (PubMed:26598617).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Non-clustered delta-protocadherins are homophilic cell adhesion molecules essential for the development of the vertebrate nervous system, as several are closely linked to neurodevelopmental disorders. Mutations in protocadherin-19 (PCDH19) result in a female-limited, infant-onset form of epilepsy (PCDH19-FE). Over 100 mutations in PCDH19 have been identified in patients with PCDH19-FE, about half of which are missense mutations in the adhesive extracellular domain. Neither the mechanism of homophilic adhesion by PCDH19, nor the biochemical effects of missense mutations are understood. Here we present a crystallographic structure of the minimal adhesive fragment of the zebrafish Pcdh19 extracellular domain. This structure reveals the adhesive interface for Pcdh19, which is broadly relevant to both non-clustered delta and clustered protocadherin subfamilies. In addition, we show that several PCDH19-FE missense mutations localize to the adhesive interface and abolish Pcdh19 adhesion in in vitro assays, thus revealing the biochemical basis of their pathogenic effects during brain development.
Structural determinants of adhesion by Protocadherin-19 and implications for its role in epilepsy.,Cooper SR, Jontes JD, Sotomayor M Elife. 2016 Oct 26;5. doi: 10.7554/eLife.18529. PMID:27787195[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Emond MR, Biswas S, Jontes JD. Protocadherin-19 is essential for early steps in brain morphogenesis. Dev Biol. 2009 Oct 1;334(1):72-83. PMID:19615992 doi:10.1016/j.ydbio.2009.07.008
- ↑ Biswas S, Emond MR, Jontes JD. Protocadherin-19 and N-cadherin interact to control cell movements during anterior neurulation. J Cell Biol. 2010 Nov 29;191(5):1029-41. PMID:21115806 doi:10.1083/jcb.201007008
- ↑ Emond MR, Biswas S, Blevins CJ, Jontes JD. A complex of Protocadherin-19 and N-cadherin mediates a novel mechanism of cell adhesion. J Cell Biol. 2011 Dec 26;195(7):1115-21. PMID:22184198 doi:10.1083/jcb.201108115
- ↑ Cooper SR, Emond MR, Duy PQ, Liebau BG, Wolman MA, Jontes JD. Protocadherins control the modular assembly of neuronal columns in the zebrafish optic tectum. J Cell Biol. 2015 Nov 23;211(4):807-14. PMID:26598617 doi:10.1083/jcb.201507108
- ↑ Tsai TY, Sikora M, Xia P, Colak-Champollion T, Knaut H, Heisenberg CP, Megason SG. An adhesion code ensures robust pattern formation during tissue morphogenesis. Science. 2020 Oct 2;370(6512):113-116. PMID:33004519 doi:10.1126/science.aba6637
- ↑ Cooper SR, Jontes JD, Sotomayor M. Structural determinants of adhesion by Protocadherin-19 and implications for its role in epilepsy. Elife. 2016 Oct 26;5. doi: 10.7554/eLife.18529. PMID:27787195 doi:http://dx.doi.org/10.7554/eLife.18529
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