Conformational stability and activity of p73 require a second helix in the tetramerization domain.
p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was...
| Autors principals: | , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Idioma: | English |
| Publicat: |
2009
|
| _version_ | 1826267612562063360 |
|---|---|
| author | Coutandin, D Löhr, F Niesen, F Ikeya, T Weber, T Schäfer, B Zielonka, E Bullock, A Yang, A Güntert, P Knapp, S McKeon, F Ou, H Dötsch, V |
| author_facet | Coutandin, D Löhr, F Niesen, F Ikeya, T Weber, T Schäfer, B Zielonka, E Bullock, A Yang, A Güntert, P Knapp, S McKeon, F Ou, H Dötsch, V |
| author_sort | Coutandin, D |
| collection | OXFORD |
| description | p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additional alpha-helix that is not present in the structure of the p53 OD. Deletion of this helix causes a dissociation of the OD into dimers; it also causes conformational instability and reduces the transcriptional activity of p73. Moreover, we show that ODs of p73 and p63 strongly interact and that a large number of different heterotetramers are supported by the additional helix. Detailed analysis shows that the heterotetramer consisting of two homodimers is thermodynamically more stable than the two homotetramers. No heterooligomerization between p53 and the p73/p63 subfamily was observed, supporting the notion of functional orthogonality within the p53 family. |
| first_indexed | 2024-03-06T20:56:52Z |
| format | Journal article |
| id | oxford-uuid:398e23c1-33f6-4a85-a15d-b7b492e434d0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:56:52Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:398e23c1-33f6-4a85-a15d-b7b492e434d02022-03-26T13:56:14ZConformational stability and activity of p73 require a second helix in the tetramerization domain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:398e23c1-33f6-4a85-a15d-b7b492e434d0EnglishSymplectic Elements at Oxford2009Coutandin, DLöhr, FNiesen, FIkeya, TWeber, TSchäfer, BZielonka, EBullock, AYang, AGüntert, PKnapp, SMcKeon, FOu, HDötsch, Vp73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additional alpha-helix that is not present in the structure of the p53 OD. Deletion of this helix causes a dissociation of the OD into dimers; it also causes conformational instability and reduces the transcriptional activity of p73. Moreover, we show that ODs of p73 and p63 strongly interact and that a large number of different heterotetramers are supported by the additional helix. Detailed analysis shows that the heterotetramer consisting of two homodimers is thermodynamically more stable than the two homotetramers. No heterooligomerization between p53 and the p73/p63 subfamily was observed, supporting the notion of functional orthogonality within the p53 family. |
| spellingShingle | Coutandin, D Löhr, F Niesen, F Ikeya, T Weber, T Schäfer, B Zielonka, E Bullock, A Yang, A Güntert, P Knapp, S McKeon, F Ou, H Dötsch, V Conformational stability and activity of p73 require a second helix in the tetramerization domain. |
| title | Conformational stability and activity of p73 require a second helix in the tetramerization domain. |
| title_full | Conformational stability and activity of p73 require a second helix in the tetramerization domain. |
| title_fullStr | Conformational stability and activity of p73 require a second helix in the tetramerization domain. |
| title_full_unstemmed | Conformational stability and activity of p73 require a second helix in the tetramerization domain. |
| title_short | Conformational stability and activity of p73 require a second helix in the tetramerization domain. |
| title_sort | conformational stability and activity of p73 require a second helix in the tetramerization domain |
| work_keys_str_mv | AT coutandind conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT lohrf conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT niesenf conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT ikeyat conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT webert conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT schaferb conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT zielonkae conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT bullocka conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT yanga conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT guntertp conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT knapps conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT mckeonf conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT ouh conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain AT dotschv conformationalstabilityandactivityofp73requireasecondhelixinthetetramerizationdomain |