|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6csu' size='340' side='right'caption='[[6csu]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='6csu' size='340' side='right'caption='[[6csu]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6csu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CSU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CSU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6csu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CSU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CSU FirstGlance]. <br> |
| - | </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=6csu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6csu OCA], [http://pdbe.org/6csu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6csu RCSB], [http://www.ebi.ac.uk/pdbsum/6csu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6csu ProSAT]</span></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]] 2.5Å</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=6csu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6csu OCA], [https://pdbe.org/6csu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6csu RCSB], [https://www.ebi.ac.uk/pdbsum/6csu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6csu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CE152_HUMAN CE152_HUMAN]] Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/CEP63_HUMAN CEP63_HUMAN]] Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/CE152_HUMAN CE152_HUMAN] Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CE152_HUMAN CE152_HUMAN]] Necessary for centrosome duplication. Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation. Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Overexpression of CEP152 can drive amplification of centrioles.<ref>PMID:21059844</ref> <ref>PMID:20852615</ref> <ref>PMID:21131973</ref> [[http://www.uniprot.org/uniprot/CEP63_HUMAN CEP63_HUMAN]] Required for normal spindle assembly. Plays a key role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication. Reported to be required for centrosomal recruitment of CEP152; however, this function has been questioned (PubMed:21983783, PubMed:26297806). Also recruits CDK1 to centrosomes (PubMed:21406398). Plays a role in DNA damage response. Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression (PubMed:21406398).<ref>PMID:21406398</ref> <ref>PMID:21983783</ref> <ref>PMID:26297806</ref> | + | [https://www.uniprot.org/uniprot/CE152_HUMAN CE152_HUMAN] Necessary for centrosome duplication. Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation. Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Overexpression of CEP152 can drive amplification of centrioles.<ref>PMID:21059844</ref> <ref>PMID:20852615</ref> <ref>PMID:21131973</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The cell is constructed by higher-order structures and organelles through complex interactions among distinct structural constituents. The centrosome is a membraneless organelle composed of two microtubule-derived structures called centrioles and an amorphous mass of pericentriolar material. Super-resolution microscopic analyses in various organisms revealed that diverse pericentriolar material proteins are concentrically localized around a centriole in a highly organized manner. However, the molecular nature underlying these organizations remains unknown. Here we show that two human pericentriolar material scaffolds, Cep63 and Cep152, cooperatively generate a heterotetrameric alpha-helical bundle that functions in conjunction with its neighboring hydrophobic motifs to self-assemble into a higher-order cylindrical architecture capable of recruiting downstream components, including Plk4, a key regulator for centriole duplication. Mutations disrupting the self-assembly abrogate Plk4-mediated centriole duplication. Because pericentriolar material organization is evolutionarily conserved, this work may offer a paradigm for investigating the assembly and function of centrosomal scaffolds in various organisms.
| + | |
| - | | + | |
| - | Molecular architecture of a cylindrical self-assembly at human centrosomes.,Kim TS, Zhang L, Il Ahn J, Meng L, Chen Y, Lee E, Bang JK, Lim JM, Ghirlando R, Fan L, Wang YX, Kim BY, Park JE, Lee KS Nat Commun. 2019 Mar 11;10(1):1151. doi: 10.1038/s41467-019-08838-2. PMID:30858376<ref>PMID:30858376</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6csu" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ahn, J I]] | + | [[Category: Ahn JI]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Kim, T S]] | + | [[Category: Kim TS]] |
| - | [[Category: Lee, E]] | + | [[Category: Lee E]] |
| - | [[Category: Lee, K S]] | + | [[Category: Lee KS]] |
| - | [[Category: Park, J E]] | + | [[Category: Park JE]] |
| - | [[Category: Zhang, L]] | + | [[Category: Zhang L]] |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Centrosome]]
| + | |
| - | [[Category: Hydrophobic]]
| + | |
| Structural highlights
Disease
CE152_HUMAN Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
CE152_HUMAN Necessary for centrosome duplication. Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation. Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Overexpression of CEP152 can drive amplification of centrioles.[1] [2] [3]
References
- ↑ Cizmecioglu O, Arnold M, Bahtz R, Settele F, Ehret L, Haselmann-Weiss U, Antony C, Hoffmann I. Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol. 2010 Nov 15;191(4):731-9. doi: 10.1083/jcb.201007107. Epub 2010 Nov , 8. PMID:21059844 doi:http://dx.doi.org/10.1083/jcb.201007107
- ↑ Dzhindzhev NS, Yu QD, Weiskopf K, Tzolovsky G, Cunha-Ferreira I, Riparbelli M, Rodrigues-Martins A, Bettencourt-Dias M, Callaini G, Glover DM. Asterless is a scaffold for the onset of centriole assembly. Nature. 2010 Oct 7;467(7316):714-8. doi: 10.1038/nature09445. Epub 2010 Sep 19. PMID:20852615 doi:http://dx.doi.org/10.1038/nature09445
- ↑ Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tuysuz B, Nurnberg G, Kiess W, Koegl M, Baessmann I, Buruk K, Toraman B, Kayipmaz S, Kul S, Ikbal M, Turner DJ, Taylor MS, Aerts J, Scott C, Milstein K, Dollfus H, Wieczorek D, Brunner HG, Hurles M, Jackson AP, Rauch A, Nurnberg P, Karaguzel A, Wollnik B. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet. 2011 Jan;43(1):23-6. doi: 10.1038/ng.725. Epub 2010 Dec 5. PMID:21131973 doi:http://dx.doi.org/10.1038/ng.725
|
